95 results
Search Results
2. Regulation of T-cell activation in the lung: isolated lung T cells exhibit surface phenotypic characteristics of recent activation including down-modulated T-cell receptors, but are locked into the G0/G1 phase of the cell cycle.
- Author
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Strickland, D., Kees, U. R., and Holt, P. G.
- Subjects
T cells ,LUNGS ,IMMUNITY ,RESPIRATORY organs ,LYMPHOCYTES ,ANTIGENS ,MACROPHAGES - Abstract
Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca
2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0 /G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]- Published
- 1996
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3. Induction of Cytotoxic T-Cell Activity by the Protective Antigen of Schistosoma mansoni Sm28GST or its Derived C-Terminal Lipopeptide.
- Author
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Pancré, V., Gras-Masse, H., Delanoye, A., Herno, J., Capron, A., and Auriault, C.
- Subjects
IMMUNIZATION ,SCHISTOSOMA mansoni ,LABORATORY mice ,T cells ,MOLECULES ,ANTIGENS ,LYMPHOCYTES ,PEPTIDES - Abstract
In a previous work the authors demonstrated that immunization with Schistosoma mansoni 28-kDa glutathion-S-transferase (Sm28GST) was able to reduce hepatic damage in infected mice and that the adoptive transfer of Sm28GST-specific T cells reproduced the protective effect obtained with the recombinant molecule. In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8
+ lymphocytes. The authors found no spontaneous CTL activity against Sm28GST-pulsed target cells during the course of the infection by S. mansoni although Sm28GST is expressed at different developmental stages of the parasite. It was observed, however, that immunization with Sm28GST is sufficient to elicit a significant level of CTL response for 6 weeks in infected mice. The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated. The authors also observe that immunization with the lipopeptidic form of the C-terminal peptide of the molecule (190-211 peptide) led to a CTL activation comparable to that observed after immunization with the whole molecule demonstrating the feasibility of using a synthetic lipopeptide as immunogen for a CTL response against Sm28GST epitopes. Moreover, like Sm28GST-specific CTLs, 190-211 lipopeptide-specific cells were also Class I MHC-restricted lymphocytes. [ABSTRACT FROM AUTHOR]- Published
- 1996
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4. A Quantitative Assay Detecting Small Numbers of Effector Helper T Cells, Regardless of Clonal Specificity.
- Author
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Pobor, G., Bandeira, A., Pettersson, S., and Coutinho, A.
- Subjects
T cells ,LYMPHOCYTES ,CELL proliferation ,IMMUNOGLOBULINS ,IMMUNOSPECIFICITY ,ANTIGENS - Abstract
We have developed a new assay for quantitative detection of all helper T cells that can induce normal B lymphocytes to proliferation and Ig secretion. To establish the optima] assay conditions, we have used cloned I helper cells of defined specificities that had previously been shown to activate normal B lymphocytes expressing the specific antigen(s) on direct cellular interactions. As shown in this paper, "irrelevant" B lymphocytes-that is, those that do not express either antigen or restriction elements recognized by the effector helper T cells-can also be induced in the presence of appropriate concentrations of pokeweed mitogen which are not mitogenic for the "target" B lymphocytes. 'Nonspecific" plaque-forming cell responses are of the same magnitude as those provided to specifically triggered targets and equal or better than those induced by lipopolysaecharide. The assay is highly sensitive and enables "semiquantitative' detection of less than 20-30 effector T cells per culture. Since effeetor helper T cells can be detected regardless of the clonal specificity, the assay appears useful for quantitative studies of various populations of T helper cells displaying mixed specificities and for the classification of cells with unknown functions. [ABSTRACT FROM AUTHOR]
- Published
- 1984
- Full Text
- View/download PDF
5. Fact and Speculation on the Function of Immune Response Genes in Antigen Presentation.
- Author
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Werdelin, O.
- Subjects
IMMUNE response ,ANTIGENS ,LYMPHOCYTES ,IMMUNOLOGY ,T cells ,LEUCOCYTES - Abstract
Immune responsiveness of guinea pigs to dinitrophenyl-poly-L-lysine and to the lysine rich random co-polymer of L-glutamic acid and L-lysine are both controlled by a single gene, the `poly-L-Iysine gene'. This paper reviews recent experiments which demonstrate that these two antigens specifically compete with one another for being presented to T cells by the same antigen-presenting cells. This finding is interpreted to mean that antigens to which responsiveness is controlled by the same single gene compete for the Ir gene product of antigen-presenting cells. The review discusses if the products of the immune response genes-presumably the Ia antigens-may constitute a third specific antigen recognition system. It further speculates if this idea may help to provide insight into the phenomenon of histocompatibility-restriction and into the nature of the mixed leucocyte reaction. [ABSTRACT FROM AUTHOR]
- Published
- 1981
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6. HLA-D/DR Restriction of Macrophage-dependent Antigen Activation of Immune T Lymphocytes: Cross-reacting Allogeneic HLA-D/DR May Partly Substitute for Self HLA-D/DR.
- Author
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Bergholtz, B. O., Thoresen, A. B., and Thorsby, E.
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MACROPHAGES ,ANTIGENS ,IMMUNITY ,T cells ,LYMPHOCYTES ,LEUCOCYTES - Abstract
Optimal proliferative response of T lymphocytes to purified protein derivative of tuberculin (PPD) in vitro requires that antigen be presented by autologous macrophages or allogeneic macrophages sharing HLA-D/DR determinants with the T cell donor. In some cases, however, T cells may respond to a limited extent to PPD in association with macrophages expressing different HLA-D/DR determinants. In this paper experiments are presented where various combinations of T cells and HLA-D/DR disparate macrophages were stimulated with PPD. We often found a strong PPD-specific response in HLA-D/DR-incompatible combinations in which the macrophages carried HLA-DR antigens known from serological studies to be cross-reactive with those of the T cell donor than in combinations in which this was not the case. Thus, the cross-reactions detected by serology may sometimes be reflected on a functional level in T lymphocyte/macrophages cooperation. [ABSTRACT FROM AUTHOR]
- Published
- 1980
- Full Text
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7. The absence of delayed-type hypersensitivity reactivity in a syngeneic murine tumour system.
- Author
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Los, G., De Weger, R. A., Mobertes, R. M., Van Loveren, H., Sakkers, R. J., and Den Otter, W.
- Subjects
DELAYED hypersensitivity ,ANTIGENS ,SEROTONIN ,T cells ,LYMPH nodes ,LYMPHOCYTES ,LABORATORY mice ,IMMUNOSUPPRESSION - Abstract
In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]
- Published
- 1987
8. Desensitization <em>in vitro</em>: the role of T-suppressor cells, T-suppressor factor and T-acceptor cells in the inhibition of the passive transfer of contact sensitivity to picryl chloride by exposure to antigen <em>in vitro</em>.
- Author
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M. Zembala, Asherson, G.L., Colizzi, V., and Watkins, Madeleine C.
- Subjects
T cells ,LYMPHOCYTES ,IMMUNITY ,IMMUNOLOGY ,ANTIGENS ,LYMPH nodes ,SPLEEN - Abstract
This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cy
r , ATx5 ), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5 , ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]- Published
- 1982
9. Absence of any male-specific antigen recognized by T lymphocytes in X/X<em>Sxr′</em> male mice.
- Author
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McLaren, A., Hunt, R., and Simpson, E.
- Subjects
CHROMOSOMES ,LYMPHOCYTES ,T cells ,TRANSPLANTATION immunology ,GRAFT rejection ,ANTIGENS - Abstract
Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection. [ABSTRACT FROM AUTHOR]
- Published
- 1988
10. Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes.
- Author
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Worel, Nina, Frank, Nelli, Frech, Christian, and Fritsch, Gerhard
- Subjects
CD34 antigen ,LYMPHOCYTES ,GRANULOCYTES ,COLONY-stimulating factors (Physiology) ,CANCER chemotherapy ,ANTIGEN analysis ,ANTIGENS ,BIOTHERAPY ,CELL differentiation ,COMBINATION drug therapy ,GRANULOCYTE-colony stimulating factor ,FLOW cytometry ,HETEROCYCLIC compounds ,T cells ,MEMBRANE glycoproteins ,LYMPHOCYTE subsets - Abstract
Background: Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens.Study Design and Methods: We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40).Results: Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA-CD133+CD34+CD38low ) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p < 0.001), whereas more differentiated subsets clearly prevailed after GP.Conclusion: In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
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11. Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome.
- Author
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Horino, Satoshi, Sasahara, Yoji, Sato, Miki, Niizuma, Hidetaka, Kumaki, Satoru, Abukawa, Daiki, Sato, Atsushi, Imaizumi, Masue, Kanegane, Hirokazu, Kamachi, Yoshiro, Sasaki, Shinya, Terui, Kiminori, Ito, Etsuro, Kobayashi, Ichiro, Ariga, Tadashi, Tsuchiya, Shigeru, and Kure, Shigeo
- Subjects
BONE marrow ,T cells ,IMMUNE system ,ANTIGENS ,BLOOD ,LYMPHOCYTES - Abstract
IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells ( Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA-matched sibling donor. We could achieve engraftment and regimen-related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+ CD25+ Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor-derived Tregs and disappearance of anti-villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor-derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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12. Intestinal DC in migrational imprinting of immune cells.
- Author
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Stock, Angus, Napolitani, Giorgio, and Cerundolo, Vincenzo
- Subjects
IMMUNE response ,ANTIGENS ,T cells ,LYMPHOCYTES ,TRETINOIN ,DENDRITIC cells - Abstract
Dendritic cells (DCs) have a pivotal role in instructing antigen-specific immune responses, processing and presenting antigens to CD4
+ and CD8+ T cells and producing factors capable to modulate the quality of T-cell responses. In this review, we will provide an historic overview on the identification of the mechanisms controlling lymphocyte migration into the largest immune organ of the body: the gut, and we will describe how in recent years an unexpected role for DCs has emerged as the architects in programming gut-homing immune cells. Specifically, we will review how intestinal DCs utilize the dietary vitamin A metabolite retinoic acid (RA) to program gut-homing lymphocytes and how intestinal DCs acquire the unique capacity to become RA producers. [ABSTRACT FROM AUTHOR]- Published
- 2013
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13. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets.
- Author
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Crozat, Karine, Guiton, Rachel, Guilliams, Martin, Henri, Sandrine, Baranek, Thomas, Schwartz-Cornil, Isabelle, Malissen, Bernard, and Dalod, Marc
- Subjects
IMMUNE system ,T cells ,LYMPHOCYTES ,ANTIGENS ,MONOCYTES - Abstract
During evolution, vertebrates have developed an adaptive immune system able to cope with a variety of pathogens. Dendritic cells (DCs) are central to this process. DCs integrate information derived from pathogens or endogenous danger signals and convey them to T lymphocytes. Most of the present knowledge on DCs was generated in mice or by using human DCs differentiated in vitro from monocytes. In both species, several DC subsets have been identified in vivo based on differences in their phenotypes, anatomical locations or functions. In mice, protective immunity against intracellular pathogens or tumors can be induced most efficiently by targeting antigens to the CD8α
+ DCs, a subset of DCs which resides in lymphoid tissues and is especially efficient at cross-presenting exogenous antigens to CD8+ T lymphocytes. In contrary, harnessing human DC subsets for medical purposes is currently hampered by insufficient knowledge about these cells. To overcome this cognitive gap, we are using comparative genomics as a tool for designing hypotheses and experiments to further characterize DC subset functions and their molecular control, including the investigation of the functional equivalences that might exist between human and mouse DC subsets. [ABSTRACT FROM AUTHOR]- Published
- 2010
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14. Variable antigen uptake due to different expression of the macrophage mannose receptor by dendritic cells in various inbred mouse strains.
- Author
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Autenrieth, Stella Eugenie and Autenrieth, Ingo Birger
- Subjects
ANTIGENS ,DENDRITIC cells ,LYMPHOCYTES ,MANNOSE ,LYMPHOID tissue ,CARRIER proteins ,T cells - Abstract
Antigen uptake by dendritic cells is essential for the induction of antigen-specific T-cell responses. Here, we investigate the ability of dendritic cells from different mouse strains to endocytose antigens. The uptake of different fluorescently labelled soluble antigens by bone marrow-derived dendritic cells from BALB/c, C57BL/6 and C3H/HeN mice was analysed by flow cytometry. Using transferrin as a specific marker for clathrin-mediated endocytosis, we observed no significant differences of transferrin uptake by dendritic cells from BALB/c, C57BL/6 and C3H/HeN mice. Similar results were obtained by analysing macropinocytosis with lucifer yellow. In contrast, analysing the uptake of ovalbumin, which is predominantly mediated by clathrin-mediated endocytosis via the macrophage mannose receptor, we found that dendritic cells from C3H/HeN mice take up three- to fivefold more ovalbumin than dendritic cells from BALB/c or C57BL/6 mice. Blocking the uptake of ovalbumin via the macrophage mannose receptor by using mannan led to a comparable uptake of ovalbumin by dendritic cells from all three mouse strains. Consistently, dendritic cells from C3H/HeN mice displayed significantly increased expression of the macrophage mannose receptor compared to dendritic cells from BALB/c or C57BL/6 mice. In conclusion, receptors involved in antigen uptake such as the macrophage mannose receptor may be differentially expressed and may explain variations of T-cell responses after vaccination in different individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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15. Fine tuning the immune response with PI3K.
- Author
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Fruman, David A. and Bismuth, Georges
- Subjects
PHOSPHOINOSITIDES ,LIPIDS ,LYMPHOCYTES ,ENZYMES ,ANTIGENS ,B cells ,T cells - Abstract
The phosphoinositide 3-kinase (PI3K) family of lipid kinases regulates diverse aspects of lymphocyte behavior. This review discusses how genetic and pharmacological tools have yielded an increasingly detailed understanding of how PI3K enzymes function at different stages of lymphocyte development and activation. Following antigen receptor engagement, activated PI3K generates 3-phosphorylated inositol lipid products that serve as membrane targeting signals for numerous proteins involved in the assembly of multiprotein complexes, termed signalosomes, and immune synapse formation. In B cells, class IA PI3K is the dominant subgroup whose loss causes profound defects in development and antigen responsiveness. In T cells, both class IA and IB PI3K contribute to development and immune function. PI3K also regulates both chemokine responsiveness and antigen-driven changes in lymphocyte trafficking. PI3K modulates the function not only of effector T cells, but also regulatory T cells; these disparate functions culminate in unexpected autoimmune phenotypes in mice with PI3K-deficient T cells. Thus, PI3K signaling is not a simple switch to promote cellular activation, but rather an intricate web of interactions that must be properly balanced to ensure appropriate cellular responses and maintain immune homeostasis. Defining these complexities remains a challenge for pharmaceutical development of PI3K inhibitors to combat inflammation and autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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16. Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk.
- Author
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Readinger, Julie A., Mueller, Kristen L., Venegas, Ana M., Reiko Horai, and Schwartzberg, Pamela L.
- Subjects
PROTEIN-tyrosine kinases ,LIVER cancer ,T cells ,LYMPHOCYTES ,BONE marrow ,ANTIGENS ,PHOSPHORYLATION - Abstract
The Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of non-receptor tyrosine kinases consists of five members: Tec, Bruton’s tyrosine kinase (Btk), inducible T-cell kinase (Itk), resting lymphocyte kinase (Rlk/Txk), and bone marrow-expressed kinase (Bmx/Etk). Although their functions are probably best understood in antigen receptor signaling, where they participate in the phosphorylation and regulation of phospholipase C-γ (PLC-γ), it is now appreciated that these kinases contribute to signaling from many receptors and that they participate in multiple downstream pathways, including regulation of the actin cytoskeleton. In T cells, three Tec kinases are expressed, Itk, Rlk/Txk, and Tec. Itk is expressed at highest amounts and plays the major role in regulating signaling from the T-cell receptor. Recent studies provide evidence that these kinases contribute to multiple aspects of T-cell biology and have unique roles in T-cell development that have revealed new insight into the regulation of conventional and innate T-cell development. We review new findings on the Tec kinases with a focus on their roles in T-cell development and mature T-cell differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
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17. CD40 regulates human dendritic cell-derived IL-7 production that, in turn, contributes to CD8+ T-cell antigen-specific expansion.
- Author
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Carreno, Beatriz M., Becker-Hapak, Michelle, and Linette, Gerald P.
- Subjects
DENDRITIC cells ,T cells ,LYMPHOCYTES ,LYMPHOID tissue ,ANTIGENS - Abstract
CD40L (CD154) expressed on activated CD4
+ T cells has been shown to provide CD40+ dendritic cells (DCs), a critical signal for establishing CD8+ T-cell immunity. CD40L–CD40 interaction leads to DC maturation with IL-12 production and upregulation of various costimulatory molecules. In this study, we show that CD40 engagement provides a unique maturation signal for human monocyte-derived DCs to upregulate IL-7 production. Other inducers of DC maturation, such as TLR 4 and TLR 7/8 agonist, fail to induce IL-7 upregulation. Neutralization of IL-7 activity in human CD8+ T-cell cultures stimulated with CMV pp65-NLV peptide-pulsed mature DCs (mDCs) leads to a reduction in antigen-specific CD8+ T-cell yields suggesting a role for mDC-derived IL-7 during T-cell receptor (TCR) activation. Furthermore, IL-7 signaling requires a temporal coordination with TCR activation for maximal antigen-specific T-cell yields. These results show that CD40 signals regulate DC-derived IL-7 production that, in turn, may instruct CD8+ T cells at the time of TCR engagement for survival leading to an increased expansion of antigen-specific T cells.Immunology and Cell Biology (2009) 87, 167–177; doi:10.1038/icb.2008.80; published online 11 November 2008 [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
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18. Signaling defects in anti-tumor T cells.
- Author
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Frey, Alan B. and Ngozi Monu
- Subjects
CANCER ,T cells ,IMMUNOSUPPRESSION ,TOLERATION ,LYMPHOCYTES ,IMMUNE response ,TUMOR growth ,ANTIGENS - Abstract
The immune response to cancer has been long recognized, including both innate and adaptive responses, showing that the immune system can recognize protein products of genetic and epigenetic changes in transformed cells. The accumulation of antigen-specific T cells within the tumor, the draining lymph node, and the circulation, either in newly diagnosed patients or resultant from experimental immunotherapy, proves that tumors produce antigens and that priming occurs. Unfortunately, just as obviously, tumors grow, implying that anti-tumor immune responses are either not sufficiently vigorous to eliminate the cancer or that anti-tumor immunity is suppressed. Both possibilities are supported by current data. In experimental animal models of cancer and also in patients, systemic immunity is usually not dramatically suppressed, because tumor-bearing animals and patients develop T-cell-dependent immune responses to microbes and to either model antigens or experimental cancer vaccines. However, inhibition of specific anti-tumor immunity is common, and several possible explanations of tolerance to tumor antigens or tumor-induced immunesuppression have been proposed. Inhibition of effective anti-tumor immunity results from the tumor or the host response to tumor growth, inhibiting the activation, differentiation, or function of anti-tumor immune cells. As a consequence, anti-tumor T cells cannot respond productively to developmental, targeting, or activation cues. While able to enhance the number and phenotype of anti-tumor T cells, the modest success of immunotherapy has shown the necessity to attempt to reverse tolerance in anti-tumor T cells, and the vanguard of experimental therapy now focuses on vaccination in combination with blockade of immunosuppressive mechanisms. This review discusses several potential mechanisms by which anti-tumor T cells may be inhibited in function. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
19. Enhancement of T cell activation by immobilized hu5C8 (anti-CD40L) monoclonal antibody.
- Author
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Arpinati, Mario, Chirumbolo, Gabriella, and Rondelli, Damiano
- Subjects
LYMPHOCYTES ,T cells ,CYTOKINES ,ANTIGENS ,INTERLEUKINS ,ANIMAL immobilization - Abstract
Background: Soluble monoclonal antibodies (MoAb) targeting CD40L on T cells can partially block T cell alloreactivity by preventing the costimulatory signal of antigen presenting cells through CD40. However, it is not known if these MoAbs can also deliver inhibiting or stimulating signals through the CD40L receptor. Materials and methods: Blood mononuclear cells were stimulated by mitogens or allogeneic stimulator cells in the presence of hu5C8 MoAb, either in soluble form, or immobilized to the culture wells. T cell responses were evaluated by means of primary and secondary mixed lymphocyte culture (MLC), cytotoxic T lymphocyte (CTL) generation, immunophenotype, apoptosis assay and cytokine release. Also, the effect of hu5C8 on cells inhibited by CTLA4-Ig was tested. Results: While the soluble hu5C8 inhibited T cell proliferation, the immobilized hu5C8 enhanced both mitogen and alloantigen-induced proliferative and cytotoxic T cell responses, without inducing further apoptotic T cell death. In the presence of CTLA4-Ig, immobilized hu5C8 increased the residual CD28-independent proliferation of alloantigen-specific T cells both in primary and secondary MLC, and prevented the inhibiting effect of CTLA4-Ig on the generation of CTL. Immobilized hu5C8 MoAb-stimulated T cells also showed a limited capacity of producing interleukin (IL)-10, even in the presence of CTLA4-Ig. Conclusions: We show that the hu5C8 MoAb has a strong mitogenic activity when immobilized, likely due to higher crosslinking capacity as compared to the soluble antibody. Strategies to induce ex-vivo T cell responses against tumor or viral antigens by means of hu5C8 MoAb antibody will be exploited based on these findings. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
20. Conventional, Regulatory, and Unconventional T Cells in the Immunologic Response to Helicobacter pylori.
- Author
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O'Keeffe, Joan and Moran, Anthony P.
- Subjects
HELICOBACTER pylori ,IMMUNE response ,NEUTROPHILS ,PLASMA cells ,EOSINOPHILS ,LYMPHOCYTES ,T cells ,IMMUNITY ,ANTIGENS - Abstract
Infection by the gastroduodenal pathogen Helicobacter pylori elicits a complex immunologic response in the mucosa involving neutrophils, plasma cells, eosinophils, and lymphocytes, of which T cells are the principal orchestrators of immunity. While so-called classical T cells (e.g. T-helper cells) that are activated by peptide fragments presented on antigen-presenting cells have received much attention in H. pylori infection, there exists a diverse array of other T cell populations that are potentially important for the outcome of the ensuing immune response, some of which have not been extensively studied in H. pylori infection. Pathogen-specific regulatory T cells that control and prevent the development of immunopathology associated with H. pylori infection have been investigated, but these cells can also benefit the bacterium in helping to prolong the chronicity of the infection by suppressing protective immune responses. An overlooked T cell population, the more recently described Th17 cells, may play a role in H. pylori-induced inflammation, due to triggering responses that ultimately lead to the recruitment of polymorphs, including neutrophils. The so-called innate or unconventional T cells, that include two conserved T cell subsets expressing invariant antigen-specific receptors, the CD1d-restricted natural killer T cells which are activated by glycolipids, and the mucosal-associated invariant T cells which play a role in defense against orally acquired pathogens in the intestinal mucosa, have only begun to receive attention. A greater knowledge of the range of T cell responses induced by H. pylori is required for a deeper understanding of the pathogenesis of this bacterium and its ability to perpetuate chronic infection, and could reveal new strategies for therapeutic exploitation. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
21. Biphenotypic bigenotypic lymphoma with simultaneous expression of PAX5/BSAP and B- and T-cell markers.
- Author
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Hansson, Markus, Jerkeman, Mats, and Dictor, Michael
- Subjects
LYMPHOMAS ,T cells ,B cells ,LYMPHOCYTES ,ANTIGENS - Abstract
Lymphomas are currently categorized according to their origin from a B or T lymphocyte. Immature and less commonly mature (peripheral) lymphomas may harbor rearrangements of both the B- and T-cell antigen receptor genes (dual genotype or bigenotype). Rarely, cells in lymphoma with a single genotype simultaneously express both B- and T-cell markers (biphenotypic lymphomas). We discuss the diagnostic and clinical implications in the case of a 42-yr-old female with a peripheral CD30
+ lymphoma that displayed both characteristic B- and T-cell surface antigens and clonal rearrangement of B- and T-cell antigen receptor gene loci. Simultaneous nuclear expression of the transcription factor gene PAX5 suggested that this major driver of B-cell differentiation did not preclude expression of CD3ε, generally assumed to be a T-cell associated antigen. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
22. Regulatory T cells in health and disease.
- Author
-
Rouse, B. T.
- Subjects
AUTOIMMUNITY ,T cells ,ANTIGENS ,IMMUNOLOGY ,LYMPHOCYTES ,IMMUNOLOGICAL tolerance - Abstract
The healthy host does not normally develop tissue destructive autoimmunity in part because of the presence of natural regulatory T cells. These cells are best identified by their expression of a unique transcription factor forkhead box transcription factor (Foxp3) that controls their regulatory function. Several other types of regulatory T cells also occur most of which are induced in response to antigen stimulation. Some of these express the Foxp3 transcription factor but many do not. The role of natural T-regulatory cells as well as induceable regulatory cells in autoimmunity, cancer, allergy and infectious disease is described. The current status of therapeutic approaches that modulate regulatory T-cell responses on the outcome of experimental animal and human disease is also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
23. T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non-allergic controls and following allergen immunotherapy.
- Author
-
Francis, J. N., Lloyd, C. M., Sabroe, I., Durham, S. R., and Till, S. J.
- Subjects
T cells ,LYMPHOCYTES ,ALLERGIC rhinitis ,RESPIRATORY allergy ,ALLERGENS ,ANTIGENS ,IMMUNOTHERAPY ,CLINICAL immunology - Abstract
Background: In T cell-associated allergic inflammation, homing of T-helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen-sensitive subjects, compared with patients on high-dose allergen injection immunotherapy (IT) and healthy controls. Methods: We examined chemokine receptor expression (CCR1–7 and CXCR1–4) by flow cytometry of peripheral blood CD4
+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme-linked immunosorbent assay. Results: On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls ( P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls ( P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen-stimulated PBMC cultures resulted in decreased interleukin (IL)-5 production compared with whole CD4+ populations ( P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL-4 and lower IFN- γ levels than CCR3− CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL-4 ( P < 0.05). Conclusion: CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen-specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
24. The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303.
- Author
-
Torikai, H., Akatsuka, Y., Miyazaki, M., Tsujimura, A., Yatabe, Y., Kawase, T., Nakao, Y., Tsujimura, K., Motoyoshi, K., Morishima, Y., Kodera, Y., Kuzushima, K., and Takahashi, T.
- Subjects
MINOR histocompatibility antigens ,GRAFT versus host disease ,LYMPHOCYTES ,T cells ,LEUCOCYTES ,ANTIGENS ,EPITOPES - Abstract
Minor histocompatibility antigens (mHags) play crucial roles in the induction of graft versus host disease (GVHD) and/or graft versus leukaemia (GVL) effects following human leucocyte antigen (HLA)-identical haematopoietic stem cell transplantation (HSCT). Using HLA-A*3101- and -A*3303-restricted cytotoxic T lymphocyte (CTL) clones generated from different post-HSCT recipients, we identified two novel mHag epitopes encoded by the leader sequence of cathepsin H (CTSH) isoform a. The nonameric sequence ATLPLLCAR was defined as an HLA-A*3101-restricted epitope (CTSH
R /A31), while a decameric peptide featuring a one N-terminal amino acid extension, WATLPLLCAR, was presented by HLA-A*3303 (CTSHR /A33). The immunogenicity of both epitopes was totally dependent on the polymorphic C-terminal arginine residue and substitution with glycine completely abolished binding to the corresponding HLA molecules. Thus, the immunogenicity of this mHag is exerted by differential HLA binding capacity. CTSH is relatively ubiquitously expressed at protein levels, thus it may be involved in GVHD and anti-leukaemic/tumour responses. Interestingly, however, CTL clones predominantly lysed targets of haematopoietic cell origin, which could not be explained in terms of the immunoproteasome system. Although the mechanisms involved in the differential susceptibility remain to be determined, these data suggest that CTSH-encoded mHags could be targets for GVL effects. [ABSTRACT FROM AUTHOR]- Published
- 2006
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- View/download PDF
25. The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology.
- Author
-
Sansom, David M. and Walker, Lucy S. K.
- Subjects
T cells ,LYMPHOCYTES ,ANTIGENS ,IMMUNITY ,IMMUNOLOGY - Abstract
The profound influence of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T-cell immunity has been known for over a decade, yet the precise roles played by these molecules still continue to emerge. Initially viewed as molecules that provide cell-intrinsic costimulatory and inhibitory signals, recent evidence suggests that both CD28 and CTLA-4 are also important in the homeostasis and function of a population of suppressive cells, termed regulatory T cells (Tregs). Here we review the main features of the CD28 and CTLA-4 system and examine how these impact upon Treg biology. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
26. Do antiviral CD8+ T cells select hepatitis C virus escape mutants? Analysis in diverse epitopes targeted by human intrahepatic CD8+ T lymphocytes.
- Author
-
Komatsu, H., Lauer, G., Pybus, O. G., Ouchi, K., Wong, D., Ward, S., Walker, B., and Klenerman, P.
- Subjects
HEPATITIS C virus ,EPITOPES ,LYMPHOCYTES ,T cells ,ANTIGENS ,IMMUNE response - Abstract
Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that – even where specific intrahepatic T cells are detectable – many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a ‘patchy’ manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between ‘selecting’ and ‘nonselecting’ intrahepatic CD8+ T-cell responses are needed in HCV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
27. Improved detection of allergen-specific T-cell responses in allergic contact dermatitis through the addition of ‘cytokine cocktails’.
- Author
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Moed, Helen, von Blomberg, Mary, Bruynzeel, Derk P., Scheper, Rik, Gibbs, Susan, and Rustemeyer, Thomas
- Subjects
T cells ,LYMPHOCYTES ,IMMUNE response ,IMMUNOLOGY ,ALLERGENS ,ANTIGENS - Abstract
Moed H, von Blomberg M, Bruynzeel DP, Scheper R, Gibbs S, Rustemeyer T. Improved detection of allergen-specific T-cell responses in allergic contact dermatitis through the addition of ‘cytokine cocktails’. The gold standard for the diagnosis of allergic hypersensitivity is skin patch testing with the suspected allergens. This diagnostic tool, however, has distinct disadvantages, and therefore the development of alternative or complementary in vitro tests is of great importance. In this study, we evaluate the applicability of an in vitro test method, as developed earlier for nickel allergy, to detect allergen-specific T cells in the blood of patients allergic to frequent sensitizers (chromate, cobalt, paraphenylenediamine, fragrances and chloromethyl-isothiazolinone). Peripheral blood mononuclear cells (PBMCs) of allergic patients and healthy controls were cultured in the absence or presence of allergen. Additionally, type 1 (IL-7 and IL-12) or type 2 (IL-7 and IL-4) stimulating cytokines were added; after 6-day proliferation, IFN-γ and IL-5 secretions were determined. Without the addition of cytokines, consistent allergen-induced proliferation was observed in PBMCs of nickel-allergic patients only. By contrast, the addition of type 1 or type 2 stimulating cytokines resulted in a significantly enhanced allergen-specific proliferation for all allergens tested (sensitivity increased from 26 to 43% or 38%, respectively, P < 0.05). In these cultures, allergen-induced IFN-γ and IL-5 secretion was also significantly increased, compared to healthy controls ( P < 0.05, for IFN-γ sensitivity 79%, specificity 93%; for IL-5 sensitivity 74%, specificity 81%). In conclusion, these results demonstrate an increased proliferative capacity and cytokine production by allergen-specific T cells from allergic patients, but not of healthy individuals upon stimulation with allergens in combination with type 1 or 2 skewing cytokines. The present data warrant further exploration of the application of this test to a broader set of allergens. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
28. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies.
- Author
-
Lohse, Louise, Nielsen, Jens, Kamstrup, Søren, Oleksiewicz, Martin B., and Eriksen, Lis
- Subjects
MONOCLONAL antibodies ,T cells ,LYMPHOCYTES ,THERAPEUTICS ,ANTIGENS ,CELLS - Abstract
Lohse L, Nielsen J, Kamstrup S, Oleksiewicz MB, Eriksen L. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies. APMIS 2005;113:489–96. In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a response. In two separate animal experiments, long-term treatment was performed with m-mAbs at low-dose levels and therapeutic levels, respectively. Two specific m-mAbs that recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T-lymphocytes) and two irrelevant control m-mAbs having no cognate antigen in the pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to quantitate the circulating m-mAbs, as well as the induced pig anti-mouse antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days after the start of m-mAb treatment with the specific m-mAbs. However, the different mAbs showed striking differences in the kinetics and levels of PAMA responses, differences that might be ascribed to the m-mAb formulation and epitope specificity. In conclusion, treatment of pigs with m-mAbs against T-cell surface antigens induced rapid PAMA responses. This may influence and possibly decrease the effect of the m-mAb treatment by narrowing the time period where m-mAbs can efficiently be used for cell depletion. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
29. Epicutaneous immunization inducesαβ T-cell receptor CD4 CD8 double-positive non-specific suppressor T cells that inhibit contact sensitivity via transforming growth factor-β.
- Author
-
Szczepanik, Marian, Bryniarski, Krzysztof, Tutaj, Monika, Ptak, Maria, Skrzeczynska, Joanna, Askenase, Philip W., and Ptak, Wlodzimierz
- Subjects
ANTIGENS ,GROWTH factors ,CYTOKINES ,IMMUNIZATION ,LYMPHOCYTES ,IMMUNOLOGY - Abstract
Since it was previously shown that protein antigens applied epicutaneously in mice induce allergic dermatitis mediated by production of T helper 2 (Th2) cytokines we postulated that this might induce suppression of Th1 immunity. Here we show that epicutaneous immunization of normal mice with a different protein antigen applied on the skin in the form of a patch induces a state of subsequent antigen-non-specific unresponsiveness caused by suppressor T cells (Ts) that inhibit sensitization and elicitation of effector T-cell responses. Suppression is transferablein vivobyαβ-T-cell receptor CD4
+ CD8+ double positive lymphocytes harvested from lymphoid organs of skin patched animals and are not major histocompatibility complex-restricted nor antigen specific. Both CD25+ and CD25– CD4+ CD8+ T cells are able to suppress adoptive transfer of Th1 effector cells mediating cutaneous contact sensitivity.In vivotreatment with monoclonal antibodies showed that the cytokines interleukin (IL)-4, IL-10 and transforming growth factor-β (TGF-β) are involved in the induction of the Ts cells. Additionally, using IL-10–/– mice we found that IL-10 is involved in skin induced tolerance. Furtherin vitroexperiments showed that lymph node cells of skin tolerized mice non-specifically suppress[3 H]thymidine incorporation by antigen-stimulated immune cells and this effect can be abolished by adding anti-TGF-β, but not anti-IL-4 nor anti-IL-10 antibodies. These studies indicate the crucial role of TGF-β in skin induced tolerance due to non-antigen-specific Ts cells and also show that IL-4, IL-10 and TGF-β play an important role in the induction of epicutaneously induced Ts cell suppression. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
30. Activated T-lymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia.
- Author
-
Papadaki, H. A., Stamatopoulos, K., Damianaki, A., Gemetzi, C., Anagnostopoulos, A., Papadaki, T., Eliopoulos, A. G., and Eliopoulos, G. D.
- Subjects
T cells ,LYMPHOCYTES ,IMMUNE system ,MACROPHAGES ,POLYMERASE chain reaction ,ANTIGENS - Abstract
To characterize the cellular components responsible for the impaired granulopoiesis in chronic idiopathic neutropenia (CIN), we investigated the origin of the proapoptotic cytokine producing cells in the bone marrow (BM) microenvironment of CIN patients. We found that the interferon gamma (IFNγ) and/or Fas-ligand expressing cells in patient BM mononuclear cells and long-term BM culture stroma cells were the CD3
+ T-lymphocytes but not the CD14+ monocytes/macrophages. The percentage of activated T-lymphocytes was increased in patients’ BM as indicated by the proportions of human leucocyte antigen (HLA)-DR+ , CD25+ , CD38+ , CD69+ and Fas+ cells within the CD3+ fraction. Intracellular IFNγ expression was higher in the BM than peripheral blood of the patients and was associated with increased BM T-lymphocyte numbers. In crossover experiments, patient CD3+ T-lymphocytes conferred autologous and allogeneic haemopoietic progenitor cell colony inhibition. Patients’ T-cell receptor repertoire and polymerase chain reaction analysis did not reveal any clonal T-lymphocyte expansion, suggesting the absence of a direct, antigen-driven recognition of CD34+ myeloid progenitor cells by patient T-lymphocytes. We conclude that CIN patients have increased number of activated T-lymphocytes in the BM, probably in the setting of a localized polyclonal immune reaction and that these cells confer an inhibitory effect on myelopoiesis through myelosuppressive cytokines including Fas-ligand and IFNγ. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
31. Generating MHC class I ligands from viral gene products.
- Author
-
Yewdell, Jonathan, Anton, Luis C., Bacik, Igor, Schubert, Ulrich, Snyder, Heidi Link, and Bennink, Jack R.
- Subjects
MAJOR histocompatibility complex ,LYMPHOCYTES ,T cells ,ANTIGENS ,ENDOPLASMIC reticulum - Abstract
MHC class I molecules function to present peptides comprised of eight to 11 residues to CD8[sup+] T lymphocytes. Here we review the efforts of our laboratory to understand how cells generate such peptides from viral gene products. We particularly focus on the nature of substrates acted on by cytosolic proteases, the contribution of proteasomes and non-proteasomal proteases to peptide generation, the involvement of ubiquitination in peptide generation, the intracellular localization of proteasome generation of antigenic peptides, and the trimming of peptides in the endoplasmic reticulum. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF
32. Increased expression of ICAM-1, E-selection, and VCAM-1 by cultured human endothelial cells upon exposure to haptens.
- Author
-
Wildner, O., Lipkow, Th., and Knop, J.
- Subjects
ALLERGENS ,ANTIGENS ,T cells ,LYMPHOCYTES ,LEUCOCYTES ,IMMUNOFLUORESCENCE - Abstract
Contact allergens induce several accessory signals which promote the activation of antigen-specific T cells. One of these signals is the increased expression of adhesion molecules on antigen-presenting cells and endothelial cells. Epicutaneous application of non-toxic doses of 2,4-dinitrofluorobenzene (DNFB) onto the skin of non-sensitized individuals elicited progressive staining for ICAM-1 on dermal microvascular endothelial cells. To elucidate the question of whether contact allergens can act directly on endothelial cells to elevate their expression of surface structures that bind leukocytes, confluent monolayers of human umbilical vein endothelial cells were incubated with the contact allergens NiSO[4sub], CoSO[4sub] or DNFB. The ICAM-1, E-selectin and HLA-DR expression were quantified by immunofluorescence flow cytometric analysis. Furthermore VCAM-1, E-selectin and ICAM-1 transcription were demonstrated by Northern blot hybridization. Constitutive ICAM-1 expression on HUVEC increased similarly to that obtained after LPS (20 μg/mI) stimulation after 4 and 24 hours of incubation with I or 2 mM NiSO[4sub] or CoSO[4sub], respectively. Pulse-stimulation with 100 or 500 nM DNFB resulted in a modest but significant increase of ICAM-1-positive cells. E-selectin and VCAM-l were not expressed on untreated HUVEC; 4 to 6 hours exposure to nickel sulfate and LPS resulted in a potent induction of E-selectin and VCAM-1 expression. DNFB and PMA had no significant influence on VCAM-l expression. None of the tested contact allergens was capable of inducing HLA-DR expression on EC at 48 to 72 hours. Enhanced expression of adhesion molecules may be an important early unspecific mechanism for induction and elicitation of a contact dermatitis. [ABSTRACT FROM AUTHOR]
- Published
- 1992
- Full Text
- View/download PDF
33. Identification of antigens which stimulate T lymphocytes of Salmonella enteritidis 11RX immunized mice.
- Author
-
Vordermeier, Hans-Martin and Kotlarski, Ieva
- Subjects
ANTIGENS ,ELECTROPHORESIS ,IMMUNOGLOBULINS ,LYMPHOCYTES ,SALMONELLA enteritidis ,T cells - Abstract
The technique of using sodium dodecylsulfate-polyacrylamide gel electrophoresis fractionated antigens (Ag) transferred to nitrocellulose filters was adopted to analyse T cell responses to Salmonella enteritidis 11RX Ag. Employing in vitro proliferation assays with T cells from S. enteritidis 11RX-primed (BALB/cXC57BL/6J)F1 mice as the measure of T cell stimulation, we have identified Ag able to stimulate T cells in the regions containing 16, 24, 34 and 50-60 kDa proteins, with dominant Ag activity at about 16kDa. These results were confirmed with long-term, Ag-specific L3T4
+ T cell lines which responded to molecules in the same four Mr regions, suggesting that no selection by a single antigenic determinant had occurred during more than 3 months of in vitro culture, or that all the molecules which were stimulatory shared at least one antigenic determinant. Because the seven clones we examined responded only to 16 kDa molecules, the former alternative is the more likely. Standard immunoblot analysis indicated that these Ag also act as major B cell stimulating determinants. T cells of BALB/c mice, which are 5-10 times more resistant to S. enteritidis 11RX than C57BL/6J mice, showed the same pattern of reactivity as F1 mice whereas the major antigenic region for T cells of C57BL/6J mice was located between 50 and 60 kDa. [ABSTRACT FROM AUTHOR]- Published
- 1990
- Full Text
- View/download PDF
34. Antigenic requirements for stimulation and target cell recognition by immune and non-immune cytotoxic T lymphocytes.
- Author
-
Owen, J. A., Grahl, K. T., Zador, A., Dorer, D. R., Klein, L., and Rubin, M. B.
- Subjects
T cells ,LYMPHOCYTES ,CELLULAR recognition ,HAPTENS ,ANTIGENS ,MICE - Abstract
The molecular requirements for recognition of antigen-modified cells by cytotoxic T lymphocyte precursors (CTLp) and their activated progeny, cytotoxic T lymphocytes (CTL). have been compared using haptenated stimulator and target cells. The antigen density requirements of T cell recognition by fluorescein-specific CTLp and CTL derived both from naive mice and from animals previously primed in vivo were determined. The cell surface hapten concentration required to stimulate CTLp cannot be distinguished from that required on target cells for lysis by their mature daughter CTL 5-7 days later. However, if the CTL (and their precursor CTLp) are derived from mice primed in vivo with hapten-conjugated cells, they require lower cell surface hapten densities for recognition than do the analogous T cell populations from naive animals. Thus, the maturation of CTLp into CTL during 5-7 days in vitro does not result in any functionally relevant change in the nature or density of antigen receptors on the surface of the T cell. This is in contrast to the apparent selection which occurs over longer time periods in vivo following priming. [ABSTRACT FROM AUTHOR]
- Published
- 1990
- Full Text
- View/download PDF
35. Presentation of Salmonella antigens by peritoneal cells of normal and Salmonella-infected mice.
- Author
-
Vordermeier, H. M., Pope, M., and Kotlarski, I.
- Subjects
SALMONELLA ,ENTEROBACTERIACEAE ,LYMPHOCYTES ,T cells ,PERITONEAL dialysis ,ANTIGENS - Abstract
A comparison of the ability of normal peritoneal cells (PC) and those harvested from mice 1-3 days after intraperitoneal immunization with live Salmonella enteritidis 11RX (11RX) to present antigen to 11RX-primed T cells was made using formalin-killed 11RX and a soluble 11RX antigen extract as antigens. Unfractionated PC and the adherent and non-adherent PC populations were analysed separately and the effects of the lysosomal function-impairing drug chloroquine and the fixative para form aldehyde, used before or after antigen-pulsing, were also determined. The results presented indicate that immunization with live 11RX did not induce any detectable modulation of APC function which could account for the ability of live 11RX to induce cell-mediated immune responses involving Lyt 2
+ T cells. [ABSTRACT FROM AUTHOR]- Published
- 1990
- Full Text
- View/download PDF
36. Functional characteristics of 197+ CD4-- CD8-- sheep T lymphocytes: Expansion and differentiation of peripheral T cells.
- Author
-
McClure, S. J. and Hein, W. R.
- Subjects
LYMPHOCYTES ,T cells ,DNA ,GENES ,LECTINS ,ANTIGENS - Abstract
This report describes the results of functional studies on the CD3
+ 197+ CD4- CD8- TCR γ/ δ+ peripheral T lymphocyte of sheep. Cell types were identified by immunofluorescent and immunoenzymic staining and separated by fluorescence activated flow cytometry. Newly synthesized DNA was labelled in vivo by incorporation of 5-bronio-2-dcoxyuridine (BrdU), and total DNA by in vitro incubation with propidium iodide. Cells were challenged in vivo with alloantigens, in vitro with alloantigens or a range of mitogens, and activation/differentiation was assessed by determination of cell number, phenotype, and thymidine incorporation. In normal lambs the 197+ cells showed no in vivo DNA synthesis except at a low level in the ileocaecal lymph node. A similarly low level of synthesis in the preseapular node was induced by local allogeneic challenge. A higher proportion of 197+ cells than of other T cells isolated from blood and lymph had G2/M phase DNA content, while very few had S phase DNA content. The response of 197+ cells in terms of change in relative numbers following in Vivo allogeneic challenge was quite different to that of CD4+ or CD8+ cells. Instead of rising to a peak at 5-8 days after challenge and then declining, the percentage of 197+ cells rose steadily with no evidence of decline by 14 days. Purified 197+ cells were activated in vitro by phytohaemagglutinin (PHA) and concanavalin-A (Con-A) but not by B cell mitogens; such activation was dependent on the inclusion of feeder cells or interleukin-2 (IL-2). PHA-induced proliferation was accompanied by altered expression of surface molecules by a proportion of the cells. Changes observed included loss of 197 antigen and gain of CD4, CD8 or MHC II antigens. In some cases coexpression of two or more of these surface antigens occurred. Thus the 197+ T-cell is as distinctive in the pattern of its functional behaviour as it is in its previously reported phenotype, distribution and ontogeny. [ABSTRACT FROM AUTHOR]- Published
- 1989
- Full Text
- View/download PDF
37. Particulate antigens may be reprocessed after initial phagocytosis for presentation to T cells in vivo.
- Author
-
Wright, M. D., Wood, P. R., Coia, G., and Cheers, C.
- Subjects
ANTIGENS ,IMMUNITY ,PHAGOCYTOSIS ,IMMUNOLOGY ,T cells ,LYMPHOCYTES - Abstract
Macrophages were pulsed with Listeria monocytogenes antigens by intraperitoneal injection prior to harvesting and thoroughly washing the cells. The pulsed macrophages were injected into the feet of Listeria-immune or naive mice to elicit a delayed hypersensitivity reaction. Where soluble Listeria antigen was used, presentation by donor macrophages to host T cells required identity within the I region of the H-2 complex. However, presentation of alcohol-killed Listeria organisms or of a living, temperature-sensitive mutant of Listeria was apparently not H-2 restricted. When T cells enriched in vitro for Listeria reactivity were injected into the feet of naive mice, they reacted in an H-2 restricted manner to antigen presented to them either by the pulsed macrophages or host cells apparently acquiring antigen from the original pulsed macrophages. [ABSTRACT FROM AUTHOR]
- Published
- 1987
- Full Text
- View/download PDF
38. LYMPHOKINES IN HEALTH AND DISEASE.
- Author
-
Krueger, Gerald C.
- Subjects
LYMPHOCYTES ,IMMUNOLOGY ,ANTIGENS ,IMMUNOGLOBULINS ,LYMPHOID tissue ,T cells - Abstract
The article presents information on Lymphokines. Clonal selection renders each of us genetically capable of recognizing a finite number of antigens. This recognition occurs either through thymus-derived lymphocytes (T Lymphocytes) or through antibody-producing lymphocytes (B lymphocytes), the former being the primary cell in cell-mediated immunity and the latter the primary cell in humoral immunity. To move from recognition of antigen by a few lymphocytes to a typical cell-mediated immune response in which many lymphocytes as well as other inflammatory cells are present.
- Published
- 1977
- Full Text
- View/download PDF
39. Strategies for modulating immunoglobulin E synthesis.
- Author
-
O'Hehir, R. E. and Lamb, J. R.
- Subjects
IMMUNOGLOBULIN E ,ANTIGENS ,T cells ,EPITOPES ,ALLERGIES ,LYMPHOCYTES - Abstract
The article focuses on strategies for modulating immunoglobulin E (IgE) synthesis. The presentation of specific antigen in a non-immunogenic form is able to induce non-responsiveness and may allow selective inactivation of T cells due to the clonal distribution of the TCR. If the disease-associated T cells that induce IgE production recognize only a limited array of determinants then this may present as an approach for the down-regulation of specific responsiveness, but structural modification of the epitopes may be necessary to remove any potential IgE binding.
- Published
- 1992
- Full Text
- View/download PDF
40. Expression of both B7-1 and CD28 contributes to the IL-2 responsiveness of CTLL-2 cells.
- Author
-
Belani, R. and Weiner, G. J.
- Subjects
INTERLEUKIN-2 ,T cells ,IMMUNOGLOBULINS ,ANTIGENS ,LYMPHOCYTES ,BIOLOGICAL assay - Abstract
The CTLL-2 bioassay is used frequently to determine interleukin-2 (IL-2) concentrations in experimental samples, including samples that contain reagents which affect the CD28-B7 interaction. We therefore evaluated whether the CD28-B7 pathway plays a role in the growth of CTLL-2 cells. Flow cytometry demonstrated that CTLL-2 cells express both CD28 and B7-1. CTLA4-immunoglobulin (CTLA4-Ig) inhibited the growth of CTLL-2 cells over a range of IL-2 concentrations, suggesting that the CD28-B7 interaction plays an important role in the growth of CTLL-2 cells. Anti-B7-1 antibody also inhibited CTLL-2 proliferation at all concentrations of IL-2. These results indicate that the CTLL-2 bioassay may not be a reliable means of determining IL-2 levels in experimental samples containing reagents that affect the CD28-B7 interaction. They also suggest that co-expression of CD28 and B7 may contribute to the growth of malignant T cells. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
41. Derivation of T-cell receptor α-chain double expresser lines from normal murine mature T cells.
- Author
-
Eshima, K., Suzuki, H., Yamazaki, S., and Shinohara, N.
- Subjects
T cell receptors ,T cells ,LYMPHOCYTES ,GENES ,IMMUNOGLOBULINS ,ANTIGENS - Abstract
Because the T-cell receptor (TCR) α-chain locus is known to lack allelic exclusion of rearrangements, and as a recent report revealed the existence of α-chain double expressers among normal human peripheral blood lymphocytes (PBL), the possible existence of TCR α-chain double expressers among mature routine T cells was examined. Although two-colour staining analysis of normal T-cell populations did not immediately reveal recognizable clusters of Vet double expressers, alternative/n vitro stimulations of normal murine T cells with antibodies to two different TCR Vα chains reproducibly induced TCR α-chain double-expresser lines. TCR complexes with different α-chains on such T cells were both shown to be functional. The cell lines were heterogeneous with respect to Vβ usage and the ratio of the expressed amounts of the two α-chains on the surface. The ratio of the two expressed α-chains was found to be very stable over a long period of time. These results are consistent with the earlier report on α-chain double expressers among human T cells and also show normal occurrence of TCR α-chain double expressers in routine T-cell populations. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
42. Induction of T-cell hyporesponsiveness by intrahepatic modulation of donor antigen-presenting cells.
- Author
-
Chung, S. W., Gorczynski, R. M., Dziadkowiec, I., and Levy, G. A.
- Subjects
T cells ,LYMPHOCYTES ,ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,CELL proliferation - Abstract
In this study, we examined the ability of varying populations of donor cells from B6 mice to induce hyporesponsiveness in T lymphocytes from C3H mice in vitro and in vivo. Small, resting B lymphocytes were inefficient stimulators of T-lymphocyte proliferation compared to splenic mononuclear cells (SMNC) and lipopolysaccharide (LPS)-induced B-cell blasts in vitro (P < 0.05). Pretreatment of SMNC with anti-B7-1 or anti-intracellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAb) similarly resulted in inefficient stimulation of T-cell proliferation in vitro (P < 0.05). However, in vivo, only intrahepatic, but not intravenous, injection of donor cells into C3H mice resulted in decreased T-lymphocyte proliferation in response to restimulation by alloantigen. This effect was most pronounced following intrahepatic injection of resting B lymphocytes or SMNC pretreated with anti-ICAM-1 mAb compared to uninjected or intravenously injected mice (P < 0.05). The hyporesponsiveness was associated with an increased production of interleukin-4 (IL-4) by the responder T lymphocytes and correlated with enhanced skin allograft survival. These data demonstrate that intrahepatic injection of donor-derived cells induces T-lymphocyte hyporesponsiveness. The mechanism appears to be modulated by an ICAM-1-mediated signal resulting in expansion of an IL-4-producing T-lymphocyte population. [ABSTRACT FROM AUTHOR]
- Published
- 1995
43. Antigen-specific human immunoglobulin production in SCID mice transplanted with human peripheral lymphocytes is dependent on CD4+ CD45RO+ T cells.
- Author
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Mártensson, C., Kristensson, K., Kalliomäki, S., Borrebaeck, C. A. K., and Carlsson, R.
- Subjects
MICE ,T cells ,SERUM ,IMMUNOGLOBULINS ,LYMPHOCYTES ,BLOOD ,IMMUNIZATION ,ANTIGENS - Abstract
Severe combined immunodeficient (SCID) mice, lacking mature T and B cells and virtually devoid of endogenous serum immunoglobulins, spontaneously produce large amounts of human immunoglobulin after transplantation with human peripheral blood lymphocytes (PBL). Moreover, after immunization with antigen an active immune response resulting in a production of specific antibodies can be induced. Here we report that human T cells must be co-transplanted with B cells into the SCID mice for immunoglobulin production to occur. Resting human B cells could be activated to immunoglobulin production in the absence of human monocytes and a specific antibody response to tetanus toxoid (TT) could be induced, suggesting that the human B cells could present antigen to T cells in the SCID environment. Production of human immunoglobulins, as well as specific antibodies, was obtained only if CD4
+ T cells of the memory phenotype, i.e. expressing CD45RO, were present. No human immunoglobulin, either of IgM or of IgG isotype, was found in SCID sera if mice were co-transplanted with human B cells and CD45RA expressing CD4+ T cells. However, FACS analysis revealed that the transplanted CD45RA+ cells became activated and differentiated towards CD45RO+ cells within 1-2 weeks. These cells also gained the lymphokine gene expression pattern associated with CD45RO+ cells, as demonstrated by polymerase chain reaction (PCR) analysis, and could support immunoglobulin production in SCID mice transplanted with fresh B cells. In fact, after differentiation of CD4+ CD45RA+ T cells towards expression of CD45RO, either in vivo in the SCID mouse or in vitro, these cells could interact with and activate human B cells to immunoglobulin production. [ABSTRACT FROM AUTHOR]- Published
- 1994
44. Expression on procine γδ lymphocytes of a phylogenetically conserved surface antigen previously restricted in expression to ruminant γδ T lymphocytes.
- Author
-
Carr, M.M., Howard, C.J., Sopp, P., Manser, J.M., and Parsons, K.R.
- Subjects
LYMPHOCYTES ,T cells ,IMMUNE system ,SWINE ,ANTIGENS ,IMMUNOLOGY ,LEUCOCYTES - Abstract
A 180,000 MW molecule has been identified on porcine leucocytes that is the homologue of the 215,000/300,000 MW WC1 (T19) leucocyte antigen previously considered to be restricted to ruminants. In ruminants the WC1 molecule is expressed by a T-cell subpopulation that is CD2
- CD4- CD8- CD5+ and that is γδ T-cell receptor positive (TcR+ ). In pigs, the 180,000 MW molecule, identified by a new monoclonal antibody CC101, is expressed by a γδ TcR+ T-cell subpopulation that is also CD2- CD4 CD8. The p180+ cells are a major T-cell subpopulation comprising approximately 40% of the peripheral blood mononuclear cells from 6-9-month-old pigs. Expression of p180 identifies the majority of the CD2- CD4- CD8- T cells in porcine blood. The p180+ T cells have a distribution in lymphoid tissues that is distinct from that oft cells that express the CD2, CD4 or CD8 molecules. They are evident particularly in the thymic medulla, the epithelium, lamina propria and interfollicular areas of the small intestine, and the superficial dermis of the skin, but largely absent from conventional T-dependent areas of secondary lymphoid tissue. [ABSTRACT FROM AUTHOR]- Published
- 1994
45. Effects of Cyclic GMP-Agonists on Ciclosporin-Induced Suppression of Human Lymphokine Production.
- Author
-
Svenson, M. and Bendtzen, K.
- Subjects
LYMPHOKINES ,LEUCOCYTES ,ANTIGENS ,T cells ,LYMPHOCYTES ,IMMUNITY - Abstract
Ciclosporin (Cs) inhibits the elaboration of the lymphokine leukocyte migration inhibitory factor (LIF) from human blood mononuclear cells (MNC) stimulated with recall antigen. This inhibition was counteracted by 3 &time; l0
-3 M dibutyryl-cyclic GMP and 8-bromo-cyclic GMP and by the cyclic GMP-agonists, sodium nitroprusside (NaNPr), ascorbic acid (As A), sodium azide (NaN3 ) and carbacholine. Using 5 &time; l0-5 M NaNPr, 1 &time; l0-3 M NaN3 , or 3 &time; 10-3 M As A1 25-50-, 4-8- and 2-3-fold elevations of MNC and T-lymphocyte cyclic GMP-levels were obtained independently of the presence of Cs. NaNPr was the most potent of these three cyclic GMP-agonists in counteracting the effect of Cs. The results indicate that intracellular cyclic GMP is a major factor involved in the reversal of Cs-induced inhibition of LIF-production. None of the cyclic GMP-analogues or -agonists by themselves possessed Interleukin 1-like activity, measured by their ability to induce LIF-production by macrophage-depleted T-lymphocytes challenged by recall antigen. [ABSTRACT FROM AUTHOR]- Published
- 1985
- Full Text
- View/download PDF
46. HLA-B27-Restricted Cytotoxic T Lymphocyte Responses to Arthritogenic Enterobacteria or Self-Antigens are Dominated by Closely Related TCRBV Gene Segments. A Study in Patients with Reactive Arthritis.
- Author
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Duchmann, R., May, E., Ackermann, B., Goergen, B., Büschenfelde, K.-H. Meyer Zum, and Märker-Hermann, E.
- Subjects
HLA histocompatibility antigens ,HISTOCOMPATIBILITY antigens ,T cells ,LYMPHOCYTES ,ANTIGENS ,ARTHRITIS - Abstract
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8
+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes with preferential rearrangement of three closely related VB families (VB 13,14,17), suggesting that these families contain a preferred site for contact with the HLA-B27 molecule. In addition, the presence of limited TCRBJ usage, limited heterogeneity in CDR3 sequences and dominant clones from individual donors among these CTL indicate that TCRB chain usage is further restricted by a limited set of peptides bound to the HLA-B27 molecule. Limited TCR usage by SF CTL of ReA patients may lay a basis for therapeutical manipulation of the T-cell response in the spondylarthropathies. [ABSTRACT FROM AUTHOR]- Published
- 1996
- Full Text
- View/download PDF
47. Responses of Human T Cells to Dominant Discrete Protein Antigens of Escherichia coli and Pseudomonas aeruginosa.
- Author
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Kersten, C. M., Mccluskey, R. T., Shaw Warren, H., and Kurnick, J. T.
- Subjects
T cells ,PSEUDOMONAS aeruginosa ,LYMPHOCYTES ,ANTIGENS ,CELL populations - Abstract
Normal human beings have circulating T lymphocytes that proliferate in response to Escherichia coli and Pseudomonas aeruginosa. We performed the present study to characterize the nature of the responding T cells and to determine whether distinct or shared conventional antigens, superantigens or polylonal activators account for T cell proliferation. Long term antigen-specific T cell lines were generated by repeated stimulation of PBMC from four donors with soluble antigen preparations of E. coli or P. aeruginosa. This resulted in the emergence of distinct T cell populations, which responded to strains of either E. coli or P. aeruginosa, but not to both. Trypsin treatment of the bacterial preparations largely eliminated their ability to stimulate the T cells. The T cell lines were predominantly CD4
+ and their proliferation to bacterial antigens was optimal using autologous APC. E. coli T cell lines proliferated not only in response to the E. coli strain with which they were initially selected, but also to four different strains of E. coli, as well as to several related Gram-negative species. P. aeruginosa selected T cells exhibited proliferative responses to six different P. aeruginosa strains, but not to the other Gram-negative species. The finding that repeated stimulation of PBMC with E. coli or P. aeruginosa leads to CD4+ T cells highly reactive with conventional protein antigens specific either for E. coli or P. aeruginosa indicates that these bacteria possess separate dominant protein antigens that drive the proliferation of peripheral blood T cells. [ABSTRACT FROM AUTHOR]- Published
- 1994
- Full Text
- View/download PDF
48. Stimulation of Peripheral Blood T Cells by an Activated T--Cell Line: a Novel Human Autologous T--T Lymphocyte Reaction.
- Author
-
Ditzian-Kadanoff, R., Parks, L., Evavold, B., Quintans, J., and Swartz, T. J.
- Subjects
T cells ,LYMPHOCYTES ,IMMUNOLOGY ,CELL culture ,ANTIGENS ,CELL communication - Abstract
T lymphocyte interactions have generally been described between described between discrete functional subsets. In our investigation of murine T-cell interactions we described a type of T-T interaction termed the 'Syngeneic T-T Lymphocyte Reaction' in which activated T-cell clones stimulated the proliferation of resting T cells mainly through a mechanism involving cell to cell contact. To investigate whether similar reactions occur in the human immune system we used the human autoreactive T-cell line C.1 to stimulate peripheral T cells. Line C.1 cells, which are not transformed and do not secrete IL2, consistently caused proliferation of purified freshly isolated autologous peripheral human T cells as measured by a [³H]-thymidine incorporation assay. The proliferation was seen in both the CD4 and CD8 subsets and could be inhibited with anti-DR and anti-CD2 antibodies. The stimulation is not due to carryove of classical antigen-presenting cells or to the C.1 line cells acting as antigen-presenting cells. We propose that some activated T cells, probably by expression of a surface molecule, can stimulate resting T cells thereby allowing for antigen-non-specific augmentation of the immune response. [ABSTRACT FROM AUTHOR]
- Published
- 1991
- Full Text
- View/download PDF
49. T Lymphocytes in Human Gut Epithelium Preferentially Express the α/β Antigen Receptor and are often CD45/UCHL1 -Positive.
- Author
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Brandtzaeg, P., Bosnes, V., Halstensen, T. S., Scott, H., Sollid, L. M., and Valnes, K. N.
- Subjects
GASTROINTESTINAL system ,T cells ,EPITHELIUM ,LYMPHOCYTES ,ANTIGENS ,CELL receptors - Abstract
A revived interest in intraepithelial lymphocytes (IEL) has been elicited by several recent reports suggesting that murine and avian intestinal epithelium contains mainly CD3
+ CD8+ cells expressing the γ/δ T-cell receptor (TcR) for antigen; this contrasts with systemically distributed T cells which preferentially employ the TcRα/β. An anatomical dichotomy in the distribution of these two T-cell lineages has hence been proposed Here we report that this concept does not hold true in man. In situ studies with monoclonal TcR-framework antibodies showed that most (70-90%) human intestinal IEL (which are mainly CD3+ CD8 ) expressed TcRα/β, Moreover, almost half of the intraepithelial CD3+ cells were positive for the smallest (180 kDa) CD45 molecule (UCHLl); this probably reflected that they are antigen-primed and thus represent traditional CD3+ CD8+ α/β+ memory T cells. [ABSTRACT FROM AUTHOR]- Published
- 1989
- Full Text
- View/download PDF
50. Self-Reactive Delayed Type Hypersensitivity Induced in Mice by Syngeneic Lymphoblasts III. Immunological Characterization of the Small and Large Antigens of the Blast Cells.
- Author
-
Klein, I. and Naor, D.
- Subjects
ANTIGENS ,IMMUNOGLOBULINS ,ENDOTOXINS ,LYMPHOCYTES ,T cells ,IMMUNE response - Abstract
X-irradiated or normal A mice injected with syngeneic concanavalin A-induced lymphoblasts (syn-Con A blasts) developed inflammatory responses in their footpads 24 to 72 h after the injection of syngeneic lipopolysaccharide-induced lymphoblasts (syn-LPS blasts) into these tissues. This response was designated syngeneic delayed type hypersensitivity (syn-DTH). The Con A blast extracts contain small (apparent MW of 6000–7000) and large (apparent MW of 160,000–175,000) syn-DTH-stimulating antigens, which are found in the total volume (low molecular weight fraction) and the void volume (high molecular weight fraction), respectively, of AcA 44 gel filtrations of this extract. The small and large antigens exhibit different immunological properties. The small antigen of A mouse lymphoblasts induced syn-DTH in X-irradiated (250 rad) mice but not in normal mice, and this immunological activity was elicited with syngeneic but not allogeneic lymphoblasts. The syn-DTH induced with the small antigen was inhibited by Lyt [This equation cannot be represented into UNICODE Entity) suppressor T cells or a factor extracted from these cells. In both normal and X-irradiated mice, and this immunological activity was elicited by both syngeneic and allogeneic LPS lymphoblasts. The small and large antigens do not immunologically cross-react, but their immunogenicity is not affected by ultraviolet irradiation, indicating that the immune response against both of them is relatively class II-independent. The possibility that the cellular autoanti-lymphoblast response observed in our studies is in fact a mechanism that down-regulates the lymphoblast activity and thus suppresses the immune response is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1988
- Full Text
- View/download PDF
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