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2. Forthcoming papers.
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IMMUNOLOGY , *T cells , *LIPOPROTEINS , *LYMPHOCYTES , *MEDICAL sciences - Abstract
A list of forthcoming papers related to immunology is presented. These include "Variable influences of iodine on the T-cell recognition of a single thyroglobulin epitope," by Hong Jiang, "Triacylated lipoproteins derived from Mycoplasma pneumoniae activate NF-jB through TLR1 and TLR2," by Takashi Shimizu, and "Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and Th1/Th2 balance," by Alexander Borowsky and Kevin Kent Lloyd.
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- 2007
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3. Forthcoming papers.
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LISTS , *LYMPHOCYTES , *COLON cancer , *GENE expression , *HISTONES - Abstract
The article presents a list of forthcoming papers in the publication. These include "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through fas ligand," "Myb proteins regulate expression of histone variant H2A.Z during thymocyte development," and "Importance of N-linked gycosylation in the functional expression of murine CD1d1."
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- 2007
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4. Forthcoming papers.
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PERIODICAL publishing , *IMMUNOLOGY , *PROSTAGLANDINS E , *LYMPHOCYTES , *COLON cancer - Abstract
A list of forthcoming papers related to immunology which are to be published is presented. They include "Prostaglandin E2 modulates dendric cell function during chlamydial genital infection," by Wei Liu and Kathleen Ann Kelly and "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through Fas ligand," by Ellen Ebert and Veronika Groh.
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- 2007
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5. Forthcoming papers.
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LYMPHOCYTES , *IMMUNOLOGY - Abstract
The article lists the forthcoming papers on immunology which includes "Prostaglandin E2 modulates dendritic cell function during chlamydial genital infection," by Wei Liu and Kathleen Ann Kelly, "Role of endogenous 4-1BB in the development of systemic lupus erythematosus," by Dass Vinjay, Jae Choi and "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through Fas ligand," by Ellen Ebert, Veronika Groh.
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- 2007
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6. Special regulatory T-cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm.
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Germain, Ronald N.
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T cells , *LYMPHOCYTES , *IMMUNOREGULATION , *SUPPRESSOR cells , *IMMUNOSUPPRESSION , *IMMUNOLOGY - Abstract
In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled ‘Infectious Immunological Tolerance’ 1 indicating that such negative regulation could be a dominant effect that prevented otherwise ‘helpful’ T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term ‘suppressor T cell’ had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed ‘regulatory T cells’, have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of ‘suppressorology’ and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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7. Forthcoming papers.
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IMMUNOLOGY , *BIBLIOGRAPHY , *DENDRITIC cells , *DEOXYRIBONUCLEOTIDES , *NUCLEOTIDES , *T cells , *LYMPHOCYTES - Abstract
The article presents a list of articles related to immunology. The articles include "Monocyte-Derived Dendritic Cells From Horses Differ From DC of Humans and Mice," by Susanne Mauel, Falko Steinbach and Hanns Ludwig, "Extended Sequence Preferences for Oligodeoxyribonucleotide Activity," by Peter Lenert, Adam Goeken and Robert Ashman, "On the Logic of Positive Selection," by Melvin Cohn, "CTLA-4 Interacts With Stat5 and Inhibits Stat5-Mediated Transcription," by M. Srahna, L. Van Grunsven, J. Remacle and Peter Vandenberghe, and "Peritoneal Macrophages Supress T Cell Activation by Amino Acid Catabolism," by R. Matlack, K. Yeh, L. Rosini, D. Gonzalez, J. Taylor, D. Silberman, A. Pennello and James Riggs.
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- 2006
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8. Forthcoming papers.
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MANUSCRIPTS , *IMMUNOLOGY , *MEDICAL sciences , *LYMPHOKINES , *LYMPHOCYTES - Abstract
The article presents information on several manuscripts that will be published in the forthcoming issues of the journal "Immunology." Some of the manuscripts enlisted are: "Resistance to Re-Challenge in the Brown Norway Rat Model of Vasculitis is Not Always Complete and May Reveal Separate Effector and Regulatory Populations," by C. S. Vinen, D. R. Turner, D. B. G. Oliveira and D. Oliveira; "Identification and Characterization of Macaque CD89," by K. A. Rogers, F. Scinicariello, R. Attanasio and Roberta Attanasio; "Th Memory Clones With Identical TCR Rearrangement (nontransgenic), But Distinct Lymphokine Phenotype, Reveals Diverse and Novel Gene Expression," by C. M. Graham, D. B. Thomas and D. Thomas.
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- 2004
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9. Concanavalin A stimulation of mouse lymphocytes at low concentration II. THE EFFECT OF CONDITIONED MEDIUM FROM PERITONEAL EXUDATE CELLS AND FROM LYMPHOCYTE CULTURES.
- Author
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Young, Barbara
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LYMPHOCYTES , *SPLEEN , *EXUDATES & transudates , *CELLS , *CELL culture , *BIOLOGICAL assay , *T cells ,MICE anatomy - Abstract
The first paper in this series reported that it was possible to reconstitute the response of low concentrations of mouse spleen lymphocytes to concanavalin A (Con A) by adding small numbers of peritoneal exudate cells (PEC) to the cultures. In this paper it is shown that the role of the PEC in this system can be partially replaced by conditioned medium (CM) prepared from PEC cultures or completely replaced by CM taken from lymphocytes cultured at optimal concentration. These CM were inactive unless fresh Con A was added to the assay cultures. Activity was present in CM which was incubated with lymphocytes or PEC for the shortest possible time but maximal activity was found after 24 hr of incubation. Activity was also found in CM prepared in the absence of Con A. Only in the case of lymphocytes cultured at optimal concentration for 24 hr was there substantially more activity in the CM thus prepared if Con A was present. PEC preparations depleted of T lymphocytes produced as much activity in CM as the untreated control. CM produced by PEC was less sensitive to heat treatment or to freezing and thawing than that produced by lymphocyte cultures. [ABSTRACT FROM AUTHOR]
- Published
- 1982
10. Immune responses in newly developed short-lived SAM mice II. SELECTIVELY IMPAIRED T-HELPER CELL ACTIVITY IN <em>IN VITRO</em> ANTIBODY RESPONSE.
- Author
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Hosokawa, T., Hosono, M., Hanada, K., Aoike, A., Kawai, K., and Takeda, T.
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T cells , *LEUCOCYTES , *IMMUNOGLOBULINS , *ANTIGENS , *LYMPHOCYTES , *CELL culture - Abstract
New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), show a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets. [ABSTRACT FROM AUTHOR]
- Published
- 1987
11. Efficient antigen presentation of soluble, but not particulate, antigen in the absence of Wiskott-Aldrich syndrome protein.
- Author
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Westerberg, Lisa, Wallin, Robert P.A., Greicius, Gediminas, Ljunggren, Hans-Gustaf, and Severinson, Eva
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B cells , *DENDRITIC cells , *CELL membranes , *LYMPHOCYTES , *BINDING sites - Abstract
B cells and dendritic cells, lacking functional Wiskott-Aldrich syndrome protein (WASP), have aberrant formation of membrane protrusions. We hypothesized that protrusions may play a role in antigen presentation, and consequently, that impaired antigen presentation may be an underlying factor of the immune deficiency in patients with Wiskott-Aldrich syndrome. In this paper, we investigated the antigen presentation capacity of B cells and dendritic cells from WASP knockout mice, using soluble and particulate antigen, to CD4[SUP+] T cells from T-cell receptor transgenic DO11.10 mice. As antigen we used soluble ovalbumin (OVA), a peptide thereof (amino acids 323-339) or bacteria expressing OVA. We tound that WASP-deficient B cells and dendritic cells efficiently processed and presented soluble OVA protein as well as its peptide in vitro, inducing proliferation and cytokine production from CD4[SUP+] T cells. Antigen presentation of soluble protein was efficient also in vivo, because immunization of WASP-deficient mice with OVA elicited proliferation of transferred, fluorescent-labelled, CD4[SUP+] T cells. Although we could detect uptake of bacteria in dendritic cells, processing and presentation of bacterial-expressed OVA was impaired in WASP-deficient dendritic cells. In conclusion, our data suggest that WASP is not needed for processing and presentation of soluble antigen, but that efficient presentation of particulate antigen require WASP. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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12. The role of hepatocyte growth factor and its receptor c-met in interactions between lymphocytes and stromal cells in secondary human lymphoid organs.
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Skibinski, G., Skibinska, A., and James, K.
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LYMPHOID tissue , *HEPATOCYTE growth factor , *GROWTH factors , *LYMPHOCYTES , *CELL differentiation - Abstract
Summary Secondary lymphoid tissue consists of two major populations of cells: lymphoid cells and stromal cells. It is generally accepted that these two cell populations influence each other however, factors mediating these processes are poorly understood. In this paper we characterize one of the possible means of communication between stroma and lymphocytes namely through hepatocyte growth factor/c-met receptor interactions. Hepatocyte growth factor (HGF) is a pleiotropic factor that is mainly produced by mesenchymal cells and acts on cells of epithelial origin which express the HGF receptor c-met. Here we demonstrate that biologically active HGF is constitutively produced by fibroblast-like stromal cells from human lymphoid tissues. HGF secretion from stromal cells was increased by direct contact with activated T cells. This increase was abrogated when activated T cells were separated physically from stromal cells. Using neutralizing antibody or cytokine inhibitors we provide evidence that enhancement of HGF production was due to additive effects of T-cell membrane-associated interleukin-1 (IL-1) and CD40 ligand. Finally, we also show that B lymphocytes activated with CD40L/anti-µ or phorbol 12-myristate 13-acetate (PMA) express c-met receptor. Co-culture of activated B cells with stromal cells from spleen leads to enhanced production of immunoglobulins. This can be partially inhibited by introduction of anti-HGF neutralizing antibodies to the culture system. Substitution of stromal cells with recombinant HGF did not produce enhancement of immunoglobulin secretion. On the other hand stimulation of c-met receptor with HGF leads to enhanced integrin-mediated adhesion of activated B cells to vascular cell adhesion molecule (VCAM-1) and fibronectin. On the basis of the above experiments we conclude that HGF production by fibroblast-like stromal cells can be modulated by activated T cells, thus providing signals for the regulation of adhesion of c-met expressing B cells to extracellular matrix proteins. In this way HGF may indirectly influence immunoglobulin secretion by B cells. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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13. Establishment of long-term CD154-dependent porcine B-cell cultures.
- Author
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Takamatsu, Andersen, Denyer, Parkhouse, and Takamatsu
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PORCINE somatotropin , *LYMPHOCYTES - Abstract
Cells of the B-cell lineage play an essential part in the immune response, not only as the producers of antigen-specific antibodies, but also as antigen-presenting cells. Unlike T cells, however, the establishment of long-term normal B-cell lines has proved to be exceedingly difficult. In this paper we demonstrate that cell membrane-expressed CD154 (CD40 ligand) is able to support the continual growth of porcine mesenteric lymph node B-cell cultures for more than 4 months without the addition of exogenous cytokines, such as interleukin-4 (IL-4). Addition of IL-4, but not interferon-γ (IFN-γ) or IL-13, to these cultures enhanced proliferation, as, to a lesser extent, did addition of IL-2. Interestingly, however, whilst IFN-γ-supplemented cultures largely consisted of immunoglobulin M (IgM)-positive cells, cultures with IL-13 or IL-4 contained a significantly increased proportion of IgG-positive cells. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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14. Enhancement of immunity against RSV-induced sarcomas by generation of hapten-reactive helper T lymphocytes.
- Author
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Comoglio, P. M., Prat, Maria, and Bretti, S.
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ROUS sarcoma , *IMMUNITY , *LYMPHOCYTES , *T cells , *TUMORS , *LABORATORY mice - Abstract
Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP)-reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors. [ABSTRACT FROM AUTHOR]
- Published
- 1985
15. Control of human T-colony formation by interleukin-2.
- Author
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Jourdan, M., Commes, T., and Klein, B.
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T cells , *LYMPHOCYTES , *INTERLEUKIN-2 , *CHROMATOGRAPHIC analysis , *IMMUNOGLOBULINS , *MONOCLONAL antibodies - Abstract
T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: (i) IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; (ii) recombinant IL-2, produced by genetically manipulated Eseherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; (iii) Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system. [ABSTRACT FROM AUTHOR]
- Published
- 1985
16. Cellular bases of the production of and response to interleukin-2 in man: role of autologous rosette-forming T-cell subsets defined with monoclonal antibodies.
- Author
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Fishbein, Eugenia, Alcocer-Varela, J., and Alarcón-Segovia, D.
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T cells , *IMMUNOGLOBULINS , *INTERLEUKIN-2 , *MONOCLONAL antibodies , *LYMPHOCYTES , *INTERLEUKINS , *SCIENTIFIC experimentation - Abstract
In this paper we present experiments that indicate that, in man, most T-celI subpopulations produce interleukin-2 (IL-2), but that the main cell subpopulation which produces it, both upon activation with phytohaemagglutinin or in autologous mixed lymphocyte cultures, is that of autologous rosette-forming (Tar) T4+ T cells. Conversely, the main IL-2-responding T-cell subpopulation is that composed of T cells depleted of Tar (T-Tar) that are T8+ IL-2 was also found to be more effectively produced by Tar cells that do not bind peanut agglutinin (PNA) than by those that do. The PNA T4+ Tar cells were also found to respond best to interleukin- I (IL-I). [ABSTRACT FROM AUTHOR]
- Published
- 1983
17. 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.
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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 (Cyr, 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
18. Migration inhibition of lymph node lymphocytes as an <em>in vitro</em> assay for cell-mediated immunity in the draining lymph nodes of parenterally immunized mice.
- Author
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Mowat, A. Mcl. and Ferguson, Anne
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LYMPHOCYTES , *LEUCOCYTES , *LYMPH nodes , *IMMUNITY , *IMMUNOLOGY - Abstract
This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMl in the mouse. [ABSTRACT FROM AUTHOR]
- Published
- 1982
19. Potentiation of natural killer cell activity of human lymphocytes <em>in vitro</em>: the participation of interferon in stimulation with <em>Staphylococcus aureus</em> Cowan I bacteria but not with Protein A.
- Author
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Kasahara, T., Harada, H., Shioiri-Nakano, K., Wakasugi, H., Imai, M., Mayumi, M., Sano, T., and Sugiura, A.
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LYMPHOCYTES , *HUMAN beings , *INTERFERONS , *IMMUNOGLOBULINS , *STIMULANTS , *STAPHYLOCOCCUS aureus - Abstract
In the previous paper we reported that human natural killer (NK) cell activity was augmented greatly by preincubation with Staphylococcus aureus Cowan I bacteria (SpA CoI) or its Protein A. We examined here whether the augmentation with these stimulants is ascribable to the direct activation of NK cells or mediated by some soluble factors produced by the stimulants. It was found that a significant amount of interferon (IFN) was produced by the SpA CoI-stimulation but not by the Protein A-stimulation, although the latter usually induced augmentation of NK-cell activity not less than SpA CoI-stimulation. IFN produced by SpA CoI was considered to belong to α-type IFN, because it was stable at pH 2.0 and could be neutralized effectively by anti-IFNα antibody. Kinetics of NK-cell activation by SpA CoI (but not by Protein A) were very similar to those by IFNα. Furthermore, augmentation of NK-cell activity with SpA CoI-stimulated supernatant was inhibited almost completely by diluted anti-IFNα antibody, whereas augmentation with Protein A-stimulated supernatant could not be abolished by the same treatment. It was, therefore, suggested that augmentation of NK-cell activity with SpA CoI might be ascribable in most part to the IFN induced, whereas Protein A can stimulate NK or T cells directly or soluble factors other than IFN might work as well. [ABSTRACT FROM AUTHOR]
- Published
- 1982
20. Anti-self receptors V. PROPERTIES OF A MOUSE SERUM FACTOR THAT BLOCKS AUTOROSETTING RECEPTORS ON LYMPHOCYTES.
- Author
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Sia, D.Y., Rylatt, D.B., and Parish, C.R.
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LYMPHOCYTES , *SERUM , *ERYTHROCYTES , *BLOOD cells , *MACROPHAGES , *MICE - Abstract
Murine lymphocytes spontaneously bind autologous and allogeneic erythrocytes via receptors that primarily recognize self H-2L molecules on the erythrocyte surface. Normal mouse serum contains a factor, termed autorosette inhibition factor (AIF), that very effectively blocks autorosette formation. This paper describes experiments that determine the origin and nature of serum AIF. It was found that AIF lacks strain and species , serum from several mammalian and nonmammalian species inhibiting the autorosetting of BALB/c thymocytes. However, mouse strains differed in the levels of AIF in their serum. Furthermore, AIF appears to directly interact with autorosetting roceptors on lymphocytes as thymocytes from the BALB/c-H-2dm2 mutant strain, which lack autorosetting receptors, were unable to absorb the factor. Several lines of experimental evidence indicated that AIF is secreted by a population of short-lived, radiosensitive macrophages (or monocytes). Firstly, in vivo administration of the anti-macrophage agents carrageenan and silica profoundly depressed AIF levels in serum. Secondly, in vitro culturing of different lymphoid cells revealed that AIF is secreted by an adherent population of peritoneal cells. Thirdly, total body irradiation experiments demonstrated that AIF production is dependent upon a radiosensitive cell that is bone marrow derived. Finally, AIF was purified to homogeneity from mouse plasma and shown to be a single polypeptide chain with a molecular weight of 84,000. [ABSTRACT FROM AUTHOR]
- Published
- 1982
21. Thymus-dependent lymphocytes of dengue virus-infected mice spleens mediate suppression through prostaglandin.
- Author
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Chaturvedi, U. C., Shukla, Manohar Indra, and Mathur, Asha
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LYMPHOCYTES , *DENGUE viruses , *SPLEEN , *ANTIGENS , *PROSTAGLANDINS , *IMMUNE response - Abstract
Our earlier observations indicate that adoptive transfer of spleen cells obtained from dengue type 2 virus (DV)-primed mice suppressed DV antigen-specific antibody secretion as detected by Jerne PFC technique. Findings of this paper indicate that the suppression was produced by non-glass-adherent cells, macrophage-depleted (by carbonyl iron) cells and by T lymphocytes of the spleen but not by the glass-adherent cells and B lymphocytes. The activity of these cells is dependent upon production of prostaglandin as shown by abrogation of their suppressor activity by pre-treatment of cells by indomethacin or aspirin which are known to block synthesis of prostaglandins. [ABSTRACT FROM AUTHOR]
- Published
- 1981
22. Characterization of immunogenic properties of haptenated liposomal model membranes in mice I. THYMUS INDEPENDENCE OF THE ANTIGEN.
- Author
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Van Houte, A. J., Snippe, H., and Willers, J. M. N.
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HAPTENS , *LIPOSOMES , *IMMUNE response , *IMMUNOGLOBULIN G , *LYMPHOCYTES , *IMMUNOLOGY - Abstract
This paper describes a rather simple coupling method for tripeptide enlarged haptens to phosphatidylethanolamine (PE) and the incorporation of these conjugates into liposomal model membranes (haptenated liposomes). These haptenated liposomes evoke a hapten-specific humoral immune response in mice. The magnitude of the response as measured by the appearance of direct plaque forming cells in the spleen is dependent on the route of immunization and the dose and epitope density of the hapten-PE derivatives. It was not possible to evoke an IgG response after either primary or secondary immunization with haptenated liposomes (as measured by the production of indirect plaques or mercaptoethanol-resistant antibody). These data, in addition to the observations that mice depleted of, or deficient in thymus-derived (T) lymphocytes respond to haptenated liposomes, indicate that these haptenated liposomes are T-cell independent antigens. [ABSTRACT FROM AUTHOR]
- Published
- 1979
23. Mechanisms of clonal abortion tolerogenesis II. CLONAL BEHAVIOUR OF IMMATURE B CELLS FOLLOWING EXPOSURE TO ANTI-μ CHAIN ANTIBODY.
- Author
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Nossal, G. J. V., Pike, Beverley L., and Battye, F. L.
- Subjects
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B cells , *IMMUNOGLOBULINS , *LYMPHOCYTES , *CLONING , *LABORATORY mice , *SPLEEN - Abstract
This paper uses B-lymphocyte cloning methods to quantify the effects of anti-μ chain antibody on immature and mature B cells. Nude mouse spleen lymphocytes were incubated with various concentrations of sheep anti-mouse μ chain antibody for times varying from 10 min to 24 h. They were then washed and plated in the agar B-cell colony formation assay. Five to six days later, control B cells had developed into colonies with a plating efficiency of about 5%. B cells from newborn mice pretreated with anti-μ yielded fewer colonies. Remarkably low concentrations sufficed to inhibit subsequent mitogenesis. For example, 3 μg/ml acting for 1 h or 0.1 μg/ml acting for 24 h gave > 50% inhibition. Adult B cells were about thirty-fold more resistant to negative signalling. Immature cells became more profoundly inhibited as anti-μ treatment was prolonged. Anti-Ia or anti-H2 antibodies, in the absence of complement, did not deliver a negative signal. Anti-μ pretreatment also reduced the capacity of immature B cells to form clones of anti-hapten antibody-forming cells in a liquid microculture system where the triggering stimulus was a T-cell independent antigen. Mature 'T-independent' B cells were not inhibited. Populations of hapten-specific B cells prepared by the hapten-gelatin method were investigated in the agar cloning system. Pretreatment of immature cells with anti-μ reduced their capacity to form colonies, this subpopulation of cells behaving like unfractionated B cells. Furthermore, hapten--HGG delivered a negative signal also. Mature hapten-specific cells or unfractionated immature spleen cells formed normal numbers of colonies following hapten HGG treatment. Overall, the studies support the view that anti-μ antibody and hapten--HGG deliver strong negative signals to immature but not mature cells with appropriate receptors. The value of anti-μ as a model, universal tolerogen was supported. Fluorescence-activated cell sorter (FACS) analysis was performed to study the relationships between functional inhibition and Ig receptor modulation. We confirmed that the IgM receptors of immature B cells are more readily modulated by anti-μ antibody than those of mature cells. Furthermore, the receptor regeneration could be partially inhibited amongst immature but not mature B cells. There was not a close quantitative relationship between the degree of modulation and the degree of functional inhibition. The results did not support the view that irreversible receptor modulation as such was the cause of functional inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 1979
24. Serological and chromatographic analyses of antigenic structures detected in human brain, thymus and lymph nodes.
- Author
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Arndt, R., Stark, Rosemarie, Klein, P., and Thiele, H.-G.
- Subjects
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THYMUS , *LYMPHOID tissue , *ENDOCRINE glands , *LYMPHOCYTES , *ANTIGENS , *BONE marrow , *CHROMATOGRAPHIC analysis , *IMMUNE system - Abstract
In the present paper it is shown that the non-species specific determinant of the antigenic thymus-brain system previously detected in murine and human brain also exists in human thymus. However, in contrast to the situation in mice and rats this antigenic structure is not expressed on suspended thymic lymphocytes, but is associated with thymic tissue largely depleted of thymic lymphocytes. Moreover, this determinant is also detectable in human lymph nodes. Besides the non-species-specific antigenic determinant human thymus and brain also share a species-specific determinant. In contrast to the non species specific determinant this structure is also displayed by suspended thymic lymphocytes, certain peripheral blood lymphocytes and bone marrow cells. The non-species-specific determinant detected in human thymus is borne by a structure, which physico-chemically resembles the thymus-brain antigen isolated from murine brain and thymus as well as from human brain. Although the structure bearing the species specific antigenic determinant has a similar apparent molecular weight both antigens could be separated by ion exchange chromatography indicating their molecular diversity. [ABSTRACT FROM AUTHOR]
- Published
- 1978
25. Lymphokine in the rat I. EVIDENCE THAT LYMPHOTOXIN ACTIVITY INVOLVES BOTH CYTOTOXIC AND STIMULATING FACTORS.
- Author
-
Ryzewska, Alicia G. and Dabrowska, Barbara K.
- Subjects
- *
LYMPHOKINES , *LYMPHOCYTES , *ANTINEOPLASTIC antibiotics , *AMINO acids , *LYMPHOID tissue , *CELL proliferation - Abstract
This paper describes experiments under-taken to determine more uniform conditions for the generation of cytotoxic lymphokine -- 'lymphotoxin' (LT) in differently stimulated rat lymphocyte cultures, and to compare the sensitivity of different test systems for detecting rat LT activity in vitro. Wistar rat lymphoid cells were activated by culture with phytohaemagglutinin (PHA) and mixed lymphocyte cultures (MLC) with semi-allogeneic (Wistar × August) F1 lymphoid cells. Lymphocyte supernatants harvested between 1 and 8 days were tested for theft effect on the metabolism and viability of cultured mouse fibroblasts (L-929 cells) by four methods: (i) inhibition of [14C]leucine incorporation; (ii) total and viable cell counts in test tube cultures ('macro test'); (iii) viable cell counts in microtitre plates ('micro test'); and (iv) chromium (51Cr) release from chromated L-cell monolayers. Cytotoxic effects on target cells of lymphocyte supernatants were evident after 3 days of PHA stimulation and 6 days of mixed lymphocyte culture, and the most sensitive indication of cytotoxic activity provided by inhibition of amino-acid incorporation and by loss of viable L cells from monolayers in tube cultures. In dilutions greater than 1:16-1:32 both cytotoxic supernatants exhibited a stimulating effect on target-cell proliferation. Stimulation of L cells growth was also observed when monolayers were exposed for 24 h to 'early' (24 h) PHA undiluted supernatants, At a later time of exposure to these supernatants a considerable loss of total and viable cells in the monolayers was evident. The results indicated that both cytotoxic and growth-stimulating lymphokines could be generated during activation of rat lymphocytes. A hypothesis is suggested whereby `lymphotoxin' activity in vitro arises from the sequential effects of stimulating and cytotoxic lymphokine, and whereby the balance of these effects in vivo might determine the response of fibroblasts involved in reactions of chronic allergic inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 1976
26. Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice.
- Author
-
Levy, Julia C., Smith, Anajane C., Whitney, R. B., McMaster, R., and Kilburn, D. G.
- Subjects
- *
T cells , *IMMUNOGLOBULINS , *CANCER in animals , *MICE as carriers of disease , *LYMPHOCYTES - Abstract
Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthreneinduced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the α and β globulins and albumin (molecular weight < 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2.5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immunoadsorbents containing goat anti-mouse immunoglobulin, and could be recovered by acid elution from the adsorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin. [ABSTRACT FROM AUTHOR]
- Published
- 1976
27. A Proposition on the Distribution of Antibody Affinities, with Implications for the Mechanism of B-cell Activation.
- Author
-
Taylor, R. B.
- Subjects
- *
ANTIGENS , *IMMUNOGLOBULINS , *B cells , *SERUM , *LYMPHOCYTES , *PLASMA cells - Abstract
For most antisera a linear relationship can be shown between log antigen concentration and the log concentration of antibody required to bind half the available antigen. This paper shows that the slope of this line, s, is related to the distribution of individual antibody clonotypes of different affinity. It is argued that the general form of the distribution approximates to exponential (rather than for example Gaussian) and that this indicates a requirement for some force to be exerted through the antigen-receptor bond in order to activate a B cell. An alternative parameter, A, which gives more weight to high affinity clonotypes, is offered in place of K0 as a measure of the avidity and biological effectiveness of an antiserum. [ABSTRACT FROM AUTHOR]
- Published
- 1975
28. The Role of Macrphages in the Cytotoxic Killing of Tumour Cells in Vitro. I. PRIMARY IMMUNIZATION OF LYMPHOCYTES IN VITRO FOR TARGET CELL KILLING AND THE MECHANISM OF LYMPHOCYTE-MACRPHAGE COOPERATION.
- Author
-
Zembala, M., Ptak, W., and Hanczakowska, Maria
- Subjects
- *
LYMPHOCYTES , *IMMUNIZATION , *CANCER cells , *CELL-mediated cytotoxicity , *LABORATORY mice , *MACROPHAGES , *CELL death , *IMMUNOLOGY - Abstract
Lymph node and spleen cells from normal mice were cultured for 3 days with polyoma virus-induced tumour, Ehrlich's ascites turnout or leukaemia L 1210 cells. This resulted in in vitro immunization of the lymphocytes, which were then transferred to irradiated target cells labelled with 51Cr. Normal, i.e. non-immune thioglycollate-stimulated peritoneal macrophages were also added to some tubes. Non-immune macrophages mixed with immunized lymphocytes showed a significantly increased ability to destroy tumour ceils as compared with macrophages in the absence of immunized lymphocytes. The immunized lymphocytes were almost entirely inactive alone. When the number of macrophages was kept constant the cytotoxicity was dependent on the number of viable immunized lymphocytes placed on the target cells. Immunized lymphocytes, in the presence of macrophages, only exhibited strong killing of the target cells against which they had been immunized; some lysis of ‘bystander’ cells was, however, seen provided specific target cells were present. Macrophage monolayers exposed to immunized lymphocytes upon contact with specific antigen became ‘armed’ and showed a significant cytotoxicity for specific target cells. When immunized lymphocytes and normal macrophages were treated with actinomycin D and puromycin, cytotoxicity was inhibited in the immunized lymphocytes but not in the macrophages. The possible mechanism of normal macrophage cooperation with immunized lymphocytes in the cytotoxic killing reaction is discussed. Results presented in this paper favour the view that immunologically specific cytophilic factor (presumptive cytophilic antibody) is involved in the macrophage-mediated cytotoxicity in the system studied. [ABSTRACT FROM AUTHOR]
- Published
- 1973
29. Characterization of a monoclonal antibody that recognizes a lymphocyte surface antigen for the cetacean homologue to CD45R.
- Author
-
De Guise, S., Erickson, K., Blanchard, M., Dimolfetto, L., Lepper, H., Wang, J., Stott, J. L., and Ferrick, D. A.
- Subjects
- *
IMMUNOGLOBULINS , *CD antigens , *LYMPHOCYTES - Abstract
As part of our current efforts to develop assays and reagents to study the immune system of marine mammals, and in view of the effort currently made to develop monoclonal antibodies to cell surface proteins of lymphocyte subsets in different species, the present paper reports on the characterization of a monoclonal antibody against the homologue of CD45R on cetacean lymphocytes. The specificity of this antibody has been characterized on the basis of immunoprecipitation of the antigen it recognized, immunoperoxidase staining on cetacean lymph node and thymus sections, as well as one and two-colour flow cytometric analysis of cetacean peripheral blood mononuclear cells and single-cell suspensions of thymus, lymph node and spleen. Anti-cetacean CD45R (F21.H) immunoprecipitated proteins of 180, 200 and 220×103 MW, with the 180×103 MW form being predominantly expressed on T cells and the 220×103 MW form expressed predominantly on B cells and thymocytes. F21.H labelled all B cells and a proportion of T cells on single-cell suspensions of spleen cells. CD45R- killer whale peripheral blood lymphocytes expressed a higher density of CD2 than CD45R+, a characteristic of memory T cells. Killer whale T lymphocytes also lost the expression of CD45R upon activation with concanavalin A (Con A) and phytohaemagglutinin (PHA). This is the first report of a monoclonal antibody to CD45R in cetaceans, and this antibody is foreseen as a possible valuable diagnostic and research tool to assess immune functions of captive and wild cetaceans as part of the evaluation of their health status. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
30. Regulation of T-cell activation in the lung: alveolar macrophages induce reversible T-cell anergy <em>in vitro</em> associated with inhibition of interleukin-2 receptor signal transduction.
- Author
-
Strickland, D., Kees, U. R., and Holt, P. G.
- Subjects
- *
T cells , *PULMONARY alveoli , *LUNGS , *MACROPHAGES , *INTERLEUKIN-2 , *LYMPHOCYTES , *RESPIRATORY organs - Abstract
Alveolar macrophages (AM) are recognized as archetypal ‘activated’ macrophages with respect to their capacity to suppress T-cell responses to antigen or mitogen, and this function has been ascribed an important role in the maintenance of local immunological homeostasis at the delicate blood: air interface. The present study demonstrates that this suppression involves a unique form of T-cell anergy, in which ‘AM-suppressed’ T cells proceed normally through virtually all phases of the activation sequence including Ca2+ flux, T-cell receptor (TCR) modulation, cytokine [including interleukin-2 (IL-2)] secretion and IL-2 receptor (IL-2R) expression. However, the ‘suppressed’ T cells fail to up-regulate CD2, and do not re-express normal levels of TCR-associated molecules after initial down-modulation; moreover, they are unable to transduce IL-2 signals leading to phosphorylation of IL-2R-associated proteins, and remained locked in G0/G1. The induction of this form of anergy is blocked by an NO-synthase inhibitor, and is reversible upon removal of AM from the T cells, which then proliferate in the absence of further stimulation. We hypothesize that this mechanism provides the means to limit the magnitude of local immune responses in this fragile tissue microenvironment, while preserving the capacity for generation of immunological memory against locally encountered antigens via clonal expansion of activated T cells after their subsequent migration to regional lymphoid organs. In an accompanying paper, we demonstrate that a significant proportion of T cells freshly isolated from lung exhibit a comparable surface phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
31. 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
-
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 Ca2+ 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
- Full Text
- View/download PDF
32. Alloantigen presentation by B cells: analysis of the requirement for B-cell activation.
- Author
-
Wilson, J. L., Cunningham, A. C., and Kirby, J. A.
- Subjects
- *
B cells , *ANTIGEN presenting cells , *LYMPHOCYTES , *CELL culture , *CELL lines , *MHC antibodies , *IMMUNOLOGY - Abstract
This paper describes a model for investigation of the functional implications of B-cell activation for antigen presentation. Mixed lymphocyte cultures were used to assess the ability of freshly isolated B cells, mitogen-activated B cells and Epstein Burr virus (EBV)-transformed B-cell lines to stimulate the activation and proliferation of allogeneic T cells under a variety of experimental conditions. It was found that resting B cells presented antigen poorly, while activated cells were highly immunogenic. Paraformaldehyde fixation completely eliminated antigen presentation by resting B cells, despite constitutive expression of class II MHC antigens. However, fixation had little effect on antigen presentation by activated B cells that expressed B7-1 and B7-2 in addition to class II major histocompatibility complex (MHC) molecules. Arrest of B-cell activation by serial fixation after treatment with F(ab′)2 fragments of goat anti-human IgM produced cells with variable antigen-presenting capacity. Optimal antigen presentation was observed for cells fixed 72hr after the initiation of B-cell activation. Although both BT-1 and B7-2 antigen expression increased after B-cell activation, it was found that the rate of T-cell proliferation correlated most closely with B7-2 expression. Stimulation of T cells by fixed activated B lymphocytes could be blocked by antibodies directed at class II MHC molecules, indicating involvement of the T-cell antigen receptor. In addition, T-cell proliferation was inhibited by antibodies specific for B7-1 and B7-2 and by the fusion protein CTLA4-Ig, demonstrating a requirement for CD28 signal transduction. The sole requirement of B7 family expression for antigen presentation by B lymphocytes was shown by demonstration of T-cell stimulation by fixed resting B cells in the presence of CD28 antibody as a source of artificial costimulation. [ABSTRACT FROM AUTHOR]
- Published
- 1995
33. A human T-cell receptor recognizes 'O' - linked sugars from the hinge region of human IgA1 and IgD.
- Author
-
Rudd, P.M., Fortune, F., Patel, T., Parekh, R.B., Dwek, R.A., and Lehner, T.
- Subjects
- *
T cells , *LYMPHOCYTES , *SUGARS , *CARBOHYDRATES , *IMMUNOGLOBULINS , *GLOBULINS - Abstract
A receptor which binds secretory lgA (sIgA) is expressed on human T cells from patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin (PHA) stimulation. The specificity of this receptor was initially probed with a panel of normal serum immunoglobulins in competitive inhibition assays with sIgA using two-colour immunofluorescence. While the receptor showed the strongest affinity for igAl (IC5010-6 M), IgD which has a similarly glycosylated hinge region to IgAl, also bound to the receptor (IC50 10-5 M). IgA2, which lacks the 'O'-glycosylated hinge region, did not significantly inhibit the binding at these concentrations suggesting that the IgA determinants for this receptor might be the oligosaccharides present in the hinge region of IgAl. IgAl has up to 10 'O'-linked oligosaccharides and four N-linked oligosaccharides per molecule. In order to probe the role of the 'O'-linked hinge sugars in the binding event, a sugar library was prepared from IgAl by a procedure designed to release 'O'-linked oligosaccharides preferentially, and to retain them in the natural closed ring formation. The sugars were released by hydrazinolysis at 65° and the resulting oligosaccharide library analysed by high voltage paper electrophoresis (HVE) and P4 gel permeation chromatography. Competitive inhibition studies demonstrated that both the library and the individual 'O'-linked sugars associated with IgA1 were implicated in the binding of IgAl to this receptor (IC50 between 1 × 10-5 M and 6 × 10-s M). Within this range the individual sugars showed small differences in their affinity for the receptor in the following order: Galβ3GalNAc = NeuNAc2α3(6)Galβ3GalNAc > NeuNAc2α3(6)Galβ3[NeuNAc2α6]GalNAc ≥ GalNAc. [ABSTRACT FROM AUTHOR]
- Published
- 1994
34. Effect of serine/threonine kinase inhibitors on motility of human lymphocytes and U937 cells.
- Author
-
Thorp, K. M., Southern, C., and Matthews, N.
- Subjects
- *
ENZYME inhibitors , *CELL migration , *CELL motility , *LYMPHOCYTES , *CELL physiology , *IMMUNOLOGY - Abstract
Mononuclear cell migration across the endothelium and through connective tissue into inflammatory sites is a multi-step process. After adhesion to the endothelium, there is an initial change in shape from spherical to irregular, followed by the migratory phase itself in which the cells constantly change in shape. In this paper we have investigated the possibility that the shape-changing in this latter phase is controlled by serine/threonine phosphorylation. For this purpose, we used a spontaneously shape- changing variant of U937 monocytoid cells as well as human peripheral blood lymphocytes that had been previously activated by anti-CD3. To test the role o f phosphorylation in shape-changing, a wide range of serine/threonine kinase inhibitors was tested, including ML-7, KT5720, KT5823, H7, H8, staurosporine, calphostin C, sphingosine, bisindolylmaleimide, chelerythrine and KN-62. Only those compounds which inhibited protein kinase C prevented lymphocyte and U937 shape-change and transmigration across polycarbonate filters. However, one specific protein kinase C inhibitor, bisindolylmaleimide, stimulated lymphocyte shape-change, [n conclusion, these studies show that activation of a serine/threonine kinase is necessary for the constant shape-changing required for motility of mononuclear cells. The kinase may be a protein kinase C isotype or a closely related enzyme. [ABSTRACT FROM AUTHOR]
- Published
- 1994
35. The targeting of T-helper cells and tumourcidal macrophages to a B-cell lymphoma using a PPD-monoclonal antibody heteroconjugate.
- Author
-
Montgomery, A. M. P., Wing, M. O., and Lachmann, P. J.
- Subjects
- *
IMMUNOGLOBULINS , *T cells , *LYMPHOCYTES , *MONOCLONAL antibodies , *LABORATORY rats , *TUBERCULIN , *BACTERIAL antigens - Abstract
This paper describes a T-cell targeting strategy based on the use of an antigen-monoclonal antibody heteroconjugate. A rat anti-idiotypic monoclonal antibody specific for a murine B-cell lymphoma was conjugated to the purified protein derivative (PPD) of tuberculin. This construct selectively delivered up to 4.5 × 104 molecules of PPD onto each tumour cell. Targeted PPD was internalized for endosomal processing and was presented in association with the I-A class II restriction element to PPD-reactive T-helper (Th) cells. Activated Th cells were demonstrated to proliferate and secrete significant levels of tumour necrosis factor (TNF). Such lymphokine secretion was observed at a PPD concentration as low as 1 ng/mI. Despite the secretion of TNF, the S-cell lymphoma was found to be resistant to autonomous Th-mediated cytotoxicity. Targeted Th cells did, however, activate tumourcidal macrophages that subsequently mediated significant tumour cytostasis. Based on this observation, it is proposed that the targeting system described may be exploited as the basis for a future immunotherapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 1992
36. Pattern of lectin binding to murine T lymphocytes.
- Author
-
Sowalsky, R. A. and Fox, B. S.
- Subjects
- *
LYMPHOCYTES , *T cells , *HEMAGGLUTININ , *IMMUNOGLOBULINS , *ACETIC acid , *GLYCINE - Abstract
Lectins can be used to detect changes in cell-surface glycosylation. In this paper we examine the lectin-binding characteristics of murine T cells as measured by flow cytometry. A large panel of labelled lectins was used to stain naive, activated and resting murine T cells. Some lectins did not detectably bind any T cells, some bound to all T cells and some bound to only a subset of splenic T cells. Three lectins which preferentially bind to previously activated T cells were identified: Bandeiraea simplicifolia BS-I, Bauhinia purpurea and Lycopersicon esculentum. In addition, two lectins were found to bind preferentially to activated T cells; Glycine max and Triticum vulgaris. Finally, no differences were found in the ability of a large panel of lectins to bind to Th1 and Th2 clones. Lectin binding may be a powerful tool for distinguishing naive, activated and memory T cells. [ABSTRACT FROM AUTHOR]
- Published
- 1992
37. Characterization of lymphocyte receptors for glycosaminoglycans.
- Author
-
Bradbury, M.G. and Parish, C.R.
- Subjects
- *
GLYCOSAMINOGLYCANS , *LYMPHOCYTES , *CELL receptors , *LYMPHOMAS , *CELL lines , *LYMPH nodes , *ERYTHROCYTES - Abstract
This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph node homing capacity. Initial binding studies with radiolabelled GAG and rosetting studies with GAG-coupled erythrocytes revealed that there are receptors on lymphocytes for the major classes of GAG (i.e. hyaluronic acid, chrondroitin sulfates, heparin), but lymphocytes bind heparin much more avidly than other GAG species. Analysis of the binding of solubilized radiolabelled cell-surface molecules to immobilized GAG revealed cell-type specific expression of GAG-binding molecules. Thus, each of four lymphoma cell lines tested gave a characteristic pattern of GAG-binding molecules, some molecules being unique to a particular cell line and others being shared by some of the lines. Similarly, splenocytes expressed at least 10 distinct GAG-binding molecules with molecular weights (MW) ranging from 10,000 to 100,000, whereas thymocytes expressed additional GAG-binding proteins of 190,000 and 250,000 MW. Furthermore, splenocytes differed from thymocytes by possessing a unique family of cell-surface molecules which reacted with each GAG. Immunoprecipitation studies demonstrated that the GAG-binding molecules on splenocytes did not correspond to any of the cell-surface antigens tested, notably the cell adhesion molecules MEL-14, CD11/CD18 and CD44, although CD8 bound weakly to heparin. Four lymphoma cell lines with well-characterized migration properties were examined for GAG-binding molecules which may control lymphocyte migration. It was found that no one GAG-binding protein could be correlated with the entry of cells into a particular lymphoid organ. Nevertheless, the role of GAG-binding molecules in the subsequent positioning of lymphocytes within lymphoid organs requires further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 1991
38. Non-random migration of CD4+, CD8+ and γδ+ T19+ lymphocytes through peripheral lymph nodes.
- Author
-
Witherden, D. A., Kimpton, W. G., Washington, E. A., and Cahill, R. N. P.
- Subjects
- *
CELL migration , *T cells , *LYMPH nodes , *LYMPHOCYTES , *LEUCOCYTES , *CELL receptors , *VASCULAR endothelium , *IMMUNOLOGY - Abstract
The experiments described in this paper have examined the migration of three fluorochrome-labelled T-lymphocyte subsets (CD4+, CD8+ and γδ+T19+) on a single passage from blood to lymph, through prescapular lymph nodes. Lymphocytes obtained from prescapular efferent lymph were labelled in vitro with fluorochrome and returned to the blood of the same animal. Over the next 2 days, lymph was continuously monitored and the cells in all collections, including the one used for intravenous infusion, were phenotyped and analysed by flow cytometry. Significant differences in the subset ratios between the infused, starting population and the recirculated population iodicated that CD4+ and γδ+T19+ lymphocytes are extracted by a resting lymph node at the same rate and that both are extracted at a faster rate than CD8+ lymphocytes. The results presented here also suggest that a unique subset of γδ+T19+ lymphocytes may be present in blood that does not recirculate through peripheral lymph nodes. [ABSTRACT FROM AUTHOR]
- Published
- 1990
39. Recirculation of lymphocyte subsets (CD5+ , CD4+ , CD8+ , T19+ and B cells) through fetal lymph nodes.
- Author
-
Kimpton, W. G., Washington, E. A., and Cahill, R. N. P.
- Subjects
- *
PHENOTYPES , *LYMPHOCYTES , *ANTIGENS , *IMMUNOGLOBULINS , *CORD blood , *IMMUNOLOGY - Abstract
The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, TI9, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas TI9+, CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of TI9+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells. [ABSTRACT FROM AUTHOR]
- Published
- 1989
40. Receptors on lymphocytes for endogenous splenic glycosaminoglycans.
- Author
-
Bradbury, M. G. and Parish, C. R.
- Subjects
- *
GLYCOSAMINOGLYCANS , *LYMPHOCYTES , *POLYSACCHARIDES , *NITROUS acid , *CELL membranes , *HEPARIN - Abstract
Previous studies have shown that lymphocytes carry cell surface receptors for sulphated polysacchar-ides (SPS), and SPS recognition may play a role in lymphocyte migration and positioning in vivo. This paper describes attempts to isolate and characterize the endogenous glycosaminoglycans (GAGs) of murine spleen and determine whether splenic lymphocytes carry cell surface receptors for these GAGS. A procedure was devised for isolating GAGs from murine spleen in good yield and high purity and the GAG preparation was then radiolabelled for subsequent binding studies. It was found that the splenic GAGs bound to murine splenocytes in a saturable, rapid and reversible manner with only a small subpopulation of the splenic GAG preparation being involved in binding. This reactive species was chondroitinase ABC-resistant and nitrous acid-sensitive, indicative of a heparan sulphate/heparin-like molecule. Furthermore, using immunofluorescent flow cytometry studies it was demonstrated that the majority of spleen cells have receptors for these GAGs. Subsequent ion- exchange fractionation and SDS-PAGE analysis of chondroitinase ABC-resistant GAGs confirmed that the splenic GAG recognized by splenocytes was a heparan sulphate/heparin molecule of approximately 20,000 MW with a binding affinity to splenocytes of approximately 5 × 10-8 M. Additional binding inhibition studies indicated two possible binding sites, for splenic GAGs on the splenocyte surface, one being fully inhibited by a range of SPS such as heparin (both coagulant and anticoagulant forms), pentosan sulphate, fucoidan, dextran sulphate, λ- and t-carrageenan, and the second being partially inhibited by κ-carrageenan. The possible relevance of these heparan sulphate! heparin receptors on splenocytes to lymphocyte positioning in vivo is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1989
41. The T-cell response to haptenated insulins II. THE ANTIBODY RESPONSE.
- Author
-
Florys, M., Wallace, G.R., Oettel, K., and Chain, B.M.
- Subjects
- *
T cells , *INSULIN , *IMMUNOGLOBULINS , *LYMPHOCYTES , *GLYCINE , *CELL proliferation - Abstract
As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently. [ABSTRACT FROM AUTHOR]
- Published
- 1989
42. Traffic and proliferative responses of recirculating lymphocytes in fetal calves.
- Author
-
Hein, W. R., Shelton, J. N., Simpson-Morgan, M. W., and Morris, B.
- Subjects
- *
THORACIC duct , *CALVES , *LYMPHOCYTES , *GESTATIONAL age , *IMMUNOGLOBULINS , *T cells , *IMMUNE system - Abstract
The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 54 to 488 ml/hr. Lymphocyte output ranged from 44 × 106 cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 × 108 cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 × 108 cells and 2 × 1010 cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. [ABSTRACT FROM AUTHOR]
- Published
- 1988
43. The absence of delayed-type hypersensitivity reactivity in a syngeneic murine tumour system.
- Author
-
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
44. Antigen-specific T-cell hyporesponsiveness in MRL congenic mice can be explained by two independent cellular defects.
- Author
-
Waterfield, J. D., Fairhurst, M., Chu, R., and Levy, J. G.
- Subjects
- *
LUPUS erythematosus , *SKIN diseases , *GENE expression , *CELL proliferation , *T cells , *LYMPHOCYTES - Abstract
MRL-+, MRL-lpr and B6-lpr have been shown to be useful models in studying systemic lupus erythematosus. MRL-lpr and B6-lpr differ from their congenic counterparts by the presence and expression of the homozygous recessive lymphoproliferation (Ipr) gene. One manifestation of this gene is a massive Tall proliferation that results in a generalized lymphadenopathy in older animals. A paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigate the basis for this hypo responsiveness in antigen-induced activation of proliferation and antibody synthesis. We have demonstrated that spleen cells from both MRL-+ and MRL-lpr mice gave minimal stimulation in a one-way mixed lymphocyte reaction against allogeneic T cells. These findings were extended to include antigen-specific proliferation involving antigen that must be processed and presented to responder lymphocytes in a H-2 restricted manner. Thus, MRL- + and MRL-lpr spleen cells pulsed with ferredoxin also failed to stimulate ferredoxin-primed T cells from B10.Br animals in vitro. We then investigated whether any T-cell defect(s) was also contributing to this proliferative hyporesponsiveness. T lymphocytes from the spleen of MRL- +, 2-month-old MRL-lpr, and 6-month-old MRL-lpr were tested in a one-way mixed lymphocyte reaction. It was found that only the MRL- + T cells gave responses approaching normal, suggesting lpr gene involvement in T-cell non-responsiveness. This was confirmed by the demonstration of an age-onset T-cell proliferative hyporesponsiveness in B6. lpr mice. This lpr gene-linked non-responsiveness was also shown to extend to T-cell helper function in a positive allogeneic effect assay. We can conclude from these studies that antigenic non-responsiveness in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr mice to provide the necessary signal(s) to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the Ip gene controlled outgrowth of a unique T-cell population that cannot respond in our assay systems. [ABSTRACT FROM AUTHOR]
- Published
- 1987
45. Effect of interferons on the inhibition of human natural killers by primary monolayer cell cultures.
- Author
-
Heiskala, M.
- Subjects
- *
INTERFERONS , *KILLER cells , *MONOMOLECULAR films , *CELL culture , *LYMPHOCYTES , *ANTIVIRAL agents - Abstract
Natural killer (NK) activity is inhibited by the contact of peripheral blood lymphocytes with primary monolayer cell cultures of both benign and malignant origin. In this study the effect of interferons (IFNs) on the inhibition has been analysed. Both αIFN- and γIFN-pretreated peripheral blood lymphocytes are effectively inhibited by monolayer target cells. IFN treatment of lymphocytes does not change cytotoxicity against the inhibitory target cells, although it enhances reactivity against NK-sensitive target cells. Treatment of monolayer cells with interferons significantly reduces their inhibitory capacity. However, diminished inhibition of NK activity by the IFN-treated target cells is not associated with increased lysis, probably due to their decreased sensitivity to natural killer cytotoxic factors (NKCF). In 18.5% of the cases studied, monolayer target cells induced endogenous IFN production in lymphocytes. in these cases no inhibition of the NK activity of the effector cells was seen. According to the results of this paper, IFNs have a dual effect on the NK regulatory system: they enhance the NK activity of the effector cells against NK-sensitive target cells, and they change the NK resistant target cells in a way that makes them less inhibitory to NK activity but simultaneously more resistant to the toxic factors secreted by NK cells. [ABSTRACT FROM AUTHOR]
- Published
- 1987
46. Antigens in Immunity XVI. A LIGHT AND ELECTRON MICROSCOPE STUDY OF ANTIGEN LOCALIZATION IN THE RAT SPLEEN.
- Author
-
Mitchell, Judith and Abbot, A.
- Subjects
- *
ANTIGENS , *SALMONELLA , *HEMOCYANIN , *CRAYFISH , *AUTORADIOGRAPHY , *MICROSCOPY , *ELECTRON microscopy , *LYMPHOCYTES , *MACROPHAGES - Abstract
This paper describes the ultrastructural location of labelled antigens and carbon in the spleens of rats from 4 minutes to 5 days after injection. Particular attention was focused on the sites of deposition 4 minutes after intra-arterial injection of microgram quantities of 125I-labelled Salmonella flagellar antigens, crayfish haemocyanin and BSA, using colloidal carbon for comparison. The combination of radioautography with both light and electron microscopy showed the importance of antigen binding by lymphocytes in the marginal zone of the spleen. Macrophage sequestration of antigens was not prominent in the spleen, although it occurred in the liver with the flagellar antigens and haemocyanin. In the spleen marginal zone, avid antigen-binding cells were found in situ 4 minutes after the injection of labelled haemocyanin. These appear to be the counterpart in vivo of antigen-binding lymphocytes prepared in vitro. Such cells also occurred infrequently after the injection of labelled polymerized flagellin, but were not found with either BSA or carbon. The apparent movement of flagellar antigen from the marginal zone to the white pulp between 1 and 2 hours after injection was seen to involve lymphocyte-associated antigen. The follicular antigen localization occurring from 1 day onwards after injection was on the dendritic reticular cells of germinal centres, as has been described in lymph nodes after subcutaneous injection. Carbon particles were rapidly sequestered in macrophages of the spleen and liver, although some particles were found between cells in the marginal zone for as long as 2 hours after injection. By 2 and 5 days, however, all the carbon was in phagocytes, even in the white pulp. Differences between the localization of antigens and carbon were clear, even in the ultrastructural sites of their location in tingible body macrophages of germinal centres. The unexpected emphasis of lymphocyte association with labelled antigens in the spleen marginal zone has allowed a revision of the mechanism previously proposed for the movement of antigens within the microenvironments of the spleen. [ABSTRACT FROM AUTHOR]
- Published
- 1971
47. Absence of any male-specific antigen recognized by T lymphocytes in X/X<em>Sxr′</em> male mice.
- Author
-
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
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