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The article presents a list of forthcoming papers related to immunology. Some of the papers include "Inhibitory p41 Isoform of Invariant Chain and Its Potential Target Enzymes Cathepsins L and H in Distinct Populations of Macrophages in Human Lymph Nodes," by V. Zavašnik-Bergant, A. Schweiger, T. Bevec, R. Golouh, V. Turk, J. Kos, and " Echinococcus Multilocularis Proliferation in Mice and Respective Parasite 14-3-3 Gene Expression is Mainly Controlled by an CD4 + T cell Mediated Immune Response," by W. Dei, A. Waidvogel, M. Siles-Lucas, Bruno Gottistein.

In the preceding paper a population of lymphoid cells was identified which (1) were derived from germinal centres in the appendix, (2) were localized in follicular structures elsewhere, and (3) could perform as antibody-forming cell precursors. The present paper presents evidence (1) that germinal centres in the spleen and lymph nodes perform the same function as germinal centres in the appendix, and (2) that germinal centres are dependent upon a stream of cells derived from the bone marrow. A new hypothesis is put forward regarding the origin and cellular kinetics of the B-cell system in mammals. It is proposed that germinal centres throughout the body function as an essentially antigen-dependent amplification system for the B-cell population of lymphocytes. Implications of this hypothesis are discussed. [ABSTRACT FROM AUTHOR]

The experiments described in this paper have examined the migration of three fluorochrome-labelled T-lymphocyte subsets (CD4+, CD8+ and gamma delta+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 indicated that CD4+ and gamma delta+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 gamma delta+T19+ lymphocytes may be present in blood that does not recirculate through peripheral lymph nodes.

This paper investigates the Vβ usage of lymph node cells from mice immunized with TNP and of cell lines made from them. In cell lines stimulated weekly with TNP in vitro for 1 month, about 87% of the cells were Vβ8+ and further analysis showed that these cells were actually Vβ.2+. This was also true for the cells that proliferated in lymph nodes in response to TNP 4 days after primary immunization, i.e. proliferation occurred mainly in the Vβ+, and in particular in the Vβ8.2+, population while much less proliferation occurred when the Vβ8- or Vβ8.2- T-cell populations are used. This was not due to non-specific damage during separation, as the response to concanavalin A and alloantigen was intact. In a separate series of experiments, mice were acutely depleted of Vβ8+ T cells by treatment with F23.1 or a control monoclonal antibody (mAb) in vivo given before immunization. Treatment with the relevant mAb virtually abolished the response to TNP. In contrast, SJL mice, which lack the gone segment coding for the Vβ8 family and several other Vβ chains, made a normal proliferative and delayed-type hypersensitivity (DTH) response to TNP. This poses the problem, which may he important in the study of the T-cell repertoire, of why acute removal of Vβ8+ T cells, which are dominantly used in the response to TNP, does not allow T cells using other chains to substitute in the response, while the absence of this population over a long period of time, because of a deletion in the genome, allows the use of T cells hearing other Vβ chains. [ABSTRACT FROM AUTHOR]

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]

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]

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]

It has been reported that, in early pregnancy in mice, there is an increase in the number of immunoglobulin-secreting cells in the lymph nodes which drain the uterus. This paper describes the results of further investigations provoked by interest in these early changes. Increases in the numbers of immunoglobulin-secreting cells were observed in syngeneically, but scarcely or not at all in allogeneically, mated mice. Increases were not observed in surgically sterilized female mice inseminated by normal males. However, subcutaneous injection of sperm provoked massive increases in the numbers of immunoglobulin-secreting cells in the lymph nodes draining the injection site. The changes were compared with those provoked by the injection of spleen cells and LPS. The results are discussed in relation to (i) the nature of the interactions provoking the increases in the number of immunoglobulin-secreting cells and their possible relationship to immunosuppression, and (ii) the relative immunological unresponsiveness which the female shows to the challenge of inseminated sperm. [ABSTRACT FROM AUTHOR]

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]

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]

Brain and thymocytes of rats, mice and fowls have certain antigenic determinants in common, which are restricted to these tissues. Among these, strain-, as well as species- and non-species-specific determinants have been detected with allotypic and heterologous antisera, respectively. With regard to the identical distribution pattern of these three different types of determinants on brain, thymus and lymph nodes it was suggested that they might belong to a common antigenic system. Using the technique of antibody-induced antigen redistribution, it is shown in the present paper that these three determinants on the thymocyte surface share a common molecular basic structure. [ABSTRACT FROM AUTHOR]

An earlier paper showed that 4 days after immunization with the contact sensitizing agent 'uxazolone' there is a peak in the percentage of cells in the draining lymph nodes that move to sites of inflammation. This was assessed by dissociating the lymph nodes, labelling them with 51Cr and injecting them into mice whose ears were painted within an hour with an unrelated contact sensitizing agent or with croton oil. The ears were then removed at about 18 hours and their radioactivity used as a measure of cell arrival. The cells that move to sites of inflammation are not macrophages as they are not removed by filtration through cotton wool. They are θ-positive and control studies show that the activity of the anti-B serum was indeed due to antibody to the θ-antigen. The cells are large and can be labelled both in vivo and in vitro with [125I]-iododeoxyuridine which is incorporated in the DNA of cells during the S phase of the cell mitotic cycle. It was concluded that the cells in immunized lymph nodes that move to sites of inflammation are T blasts. The unitary hypothesis is put forward that following immunization for delayed hypersensitivity a particular class of T cells proliferates and gives rise to large pyroninophilic blast cells; and that these cells or their immediate descendants possess the properties, either at the same time or at closely related times, of' movement to sites of inflammation and non-specific cytotoxicity as well as the capacity to passively transfer cellular immunity. [ABSTRACT FROM AUTHOR]

The ability of spleen, lymph node and peripheral blood lymphocytes to produce antibody against sheep red blood cells is decreased following administration of heterologous anti-lymphocyte serum (ALS). Cells located within the thymus are unaffected while marrow cells are affected in varying degrees, depending on the ALS used. immunological competence is restored to the marrow cell population of an ALS-treated animal before there is any significant repair of the immunological deficits which are present in its spleen, lymph node and peripheral blood lymphocyte populations. For this and other reasons it is suggested that these deficits are repaired by migration of cells from the ALS-treated animal's own thymus and marrow. The rates at which they are repaired appear to be retarded by the presence of Lee heterologous immunosuppressive antibody in the animal's circulation, and the degree of retardation seems to be directly proportional to the potency of the immunosuppressive material present and the duration for which it remains in the circulation. [ABSTRACT FROM AUTHOR]

Conventional dendritic cells (cDCs) arise from committed precursor dendritic cells (pre‐DCs) in the bone marrow that continuously seed the periphery. Pre‐DCs and other upstream progenitors proliferate and mature in response to Fms‐related receptor tyrosine kinase 3 ligand, which is considered the key cytokine for cDC development. However, other cytokines such as stem cell factor and colony‐stimulating factor 1 (CSF1) were also shown to induce pre‐DC maturation into DC‐like cells. Yet, it is still only incompletely understood which cells contribute to cDC development once pre‐DCs arrive in peripheral tissues. Here, we analysed the impact of lymph node (LN) fibroblastic stromal cells (FSCs) on the maturation of pre‐DCs into cDC‐like cells. We could demonstrate that ex vivo isolated LN FSCs co‐cultured with pre‐DCs induce precursor maturation into DC‐like cells, which were capable of efficiently promoting the proliferation of naïve CD4+ T cells. Interestingly, FSCs isolated from distinct LNs induced DC‐like cells with highly comparable transcriptomes, characterized by the expression of signature genes of both ex vivo isolated DCs and macrophages. Finally, by performing supplementation and receptor blocking studies, we could demonstrate that CSF1 is a driving factor for LN FSC‐mediated pre‐DC maturation into DC‐like cells. In summary, we could identify CSF1 as a stromal cell‐derived factor that has the potential to support the maturation of pre‐DCs into cDC‐like cells within secondary lymphoid organs. [ABSTRACT FROM AUTHOR]

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 CMI in the mouse.

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 chromotography indicating their molecular diversity.

The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, T19, 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 T19+, 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 T19+ 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.

Prostaglandin E2 (PGE2) can mediate changes in lymphocyte traffic through lymph nodes. By measuring PGE2 levels in efferent lymph from cannulated sheep lymph nodes it was shown that increased synthesis of PGE2 always correlated with cell shutdown; infusion of PGE2 alone induced cell shutdown and inhibition of PGE2 synthesis by the node abolished cell shutdown induced by antigen. [ABSTRACT FROM AUTHOR]

In normal CBA/H mice implanted under the kidney capsule with eight CBA/H.T6T6 neonatal thymus lobes it was observed that the percentage of marked thymus-graft derived T cells in the periphery, after building up to a peak, showed a biphasic exponential decline. The initial decline was very rapid and appeared to be due to loss of the thymus-graft derived cells from the system. The later decline was slower and was the same as that of an introduced cohort of lymph-node lymphocytes. The second rate of decline was, however, considerably more rapid than that of a lymph-node cohort in non thymus-grafted mice. We conclude that in multiply thymus-grafted mice the flow of cells through the T-cell pool is more rapid than in normal mice and that in this sense the thymus can be thought to drive the lymphoid system. [ABSTRACT FROM AUTHOR]

Lymph node cells from immunized rabbits were cultured with varying concentrations of antigen in preheated (56°, 30 minutes) autologous serum which had been collected before immunization. [3H]Thymidine was present for the last 6 hours of the 24-hour culture period and the radioactive labelling of acid-precipitable material was then determined. Changes in labelling due to variations of culture conditions were interpreted according to whether they were specific for control or antigen-treated cultures or non-specific. Cell concentration and serum concentration were predominantly non-specific variables influencing the labelling in control and antigen-treated cultures to a proportionate extent. However, at serum concentrations below 5 per cent labelling was disproportionately inhibited in antigen-treated cultures; there were further minor disproportionate inhibitions at higher serum concentrations. Labelling was inhibited by increasing the concentration of serum from 25 to 50 per cent, mainly due to a non-diffusible competitive inhibitory activity. Isotope-dilution analysis of the effects of serum on labelling over a wide range of serum concentrations indicated that the relationship was a complex one with at least three step-wise stimulations of the maximum labelling rate being produced by increasing the serum concentrations from 0 to 25 per cent. Labelling in antigentreated cultures containing post-immunization serum was less than labelling in cultures containing an equal volume of preimmunization serum, but labelling in control cultures was enhanced by post-immunization serum. These results are shown to be compatible with the proposals (i) that labelling in control cultures reflects the response of cells to low concentrations of endogenous antigens, and (ii) that preimmunization serum and post-immunization serum contain ‘natural’ and ‘acquired’ antibodies respectively, which normally buffer cell-borne receptor sites against reaction with endogenous and exogenous antigens. [ABSTRACT FROM AUTHOR]

The injection of sheep red cells and capsular antigen of Pasteurella pestis leads to increase in the absolute and relative number of plasma cells in the draining lymph node and spleen. An equation is proposed which is compatible with the linear relationship which is observed between the logarithm of the antigen dose and the square root of the number of plasma cells. An index of homogeneity is derived from this equation which is related to the number of different antigenic determinants and different antigenic molecules in the immunogen. This index varied in the predicted way when mice were immunized with relatively pure and crude preparations of capsular antigen. [ABSTRACT FROM AUTHOR]

Lymph node cells from Black Hooded (BH) rats immunized with Freund's complete adjuvant (CFA) are only poorly cytotoxic to target cells treated with target cell specific antibody. Normal spleen cells are highly cytotoxic to antibody coated target cells. When 106 lymph node cells, from rats immunized with Chang cells in CFA, are mixed with 107 spleen cells from unimmunized rats, the mixture is 8.6 times more cytotoxic than the sum of the cytotoxicities of the two lymphoid cell populations alone. Immune lymph node cells were no more cytotoxic in the presence of 5 per cent fresh guinea-pig serum than in the presence of heat inactivated guinea-pig serum. Immune spleen cells are prevented from damaging target cells by antagonists of protein synthesis such as Puromycin. Puromycin, however, does not alter the cytotoxic effect of either immune or nonimmune spleen cells on antibody coated target cells. From these experiments it is tentatively suggested that lymphoid cells from immunized animals mediate target cell damage by a reaction involving firstly immunologically specific responder cells which synthesise antibody and secondly non-specific effector cells which damage the antibody coated target cells. Evidence is presented which suggests that stable soluble factors may not be responsible for mediating target cell damage in this system. [ABSTRACT FROM AUTHOR]

Single lymph node cells from animals producing anti-T6 were incubated in microdrops together with test phages T2 and T4, which are serologically related to T6. In many of the drops complete or partial inactivation of the test phages was observed. While the ratio anti-T2 : anti-T4 in microdrops containing a known low concentration of anti-T6 serum antibody always remained constant, the post-incubation ratio in different single-cell droplets varied greatly. Since immunological inactivation of the T even phages seems to be mainly caused by the tail-fibre anti-fibre interaction, the results indicate that different cells make different antibodies to the fibre protein of T6. [ABSTRACT FROM AUTHOR]

Summary: Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti‐bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology. We will try to explain this in the context of intestinal secretory antibodies (mainly secretory IgA), which have been described to prevent, to alter, to not affect, or to promote colonization of the intestine and gut‐draining lymphoid tissues, and where effector mechanisms have remained elusive. In fact, these apparently contradictory outcomes can be generated by combining the basic premises of bacterial agglutination with an understanding of bacterial growth (i.e. secretory IgA‐driven enchained growth), fluid handling and bacterial competition in the gut lumen. [ABSTRACT FROM AUTHOR]

Summary: An increasing body of literature supports a role for neutrophils as players in the orchestration of adaptive immunity. During acute and chronic inflammatory conditions, neutrophils rapidly migrate not only to sites of inflammation, but also to draining lymph nodes and spleen, where they engage bidirectional interactions with B‐ and T‐lymphocyte subsets. Accordingly, a relevant role of neutrophils in modulating B‐cell responses under homeostatic conditions has recently emerged. Moreover, specialized immunoregulatory properties towards B or T cells acquired by distinct neutrophil populations, originating under pathological conditions, have been consistently described. In this article, we summarize the most recent data from human studies and murine models on the ability of neutrophils to modulate adaptive immune responses under physiological and pathological conditions and the mechanisms behind these processes. In this article, we summarize the most recent data from human studies and murine models on the ability of neutrophils to modulate B‐ and T‐cell responses under physiological and pathological conditions and the mechanisms behind these processes. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3+ regulatory T cells to regulate immune responses to beneficial or non-harmful agents in the intestine, such as commensal bacteria and foods. Several studies in MLN DCs have revealed that the CD103+ DC subset highly induces regulatory T cells, and another study has reported that MLN DCs from programmed death ligand 1 (PD-L1) -deficient mice could not induce regulatory T cells. Hence, the present study investigated the expression of these molecules on MLN CD11c+ cells. Four distinct subsets expressing CD103 and/or PD-L1 were identified, namely CD11b+ CD103+ PD-L1High, CD11b− CD103+ PD-L1High, CD11b− CD103+ PD-L1Low and CD11b+ CD103− PD-L1Int. Among them, the CD11b− CD103+ PD-L1High DC subset highly induced Foxp3+ T cells. This subset expressed Aldh1a2 and Itgb8 genes, which are involved in retinoic acid metabolism and transforming growth factor- β (TGF- β) activation, respectively. Exogenous TGF- β supplementation equalized the level of Foxp3+ T-cell induction by the four subsets whereas retinoic acid did not, which suggests that high ability to activate TGF- β is determinant for the high Foxp3+ T-cell induction by CD11b− CD103+ PD-L1High DC subset. Finally, this subset exhibited a migratory DC phenotype and could take up and present orally administered antigens. Collectively, the MLN CD11b− CD103+ PD-L1High DC subset probably takes up luminal antigens in the intestine, migrates to MLNs, and highly induces regulatory T cells through TGF- β activation. [ABSTRACT FROM AUTHOR]

CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic ( NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD- SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4+ CD25+ Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity. [ABSTRACT FROM AUTHOR]

Myeloid dendritic cells ( mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the m DC response, particularly early in acute infection, is ill-defined. We studied acute pathogenic simian immunodeficiency virus ( SIV) infection of rhesus macaques to address this question. The m DC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response. In lymph nodes, m DC were apoptotic, activated and proliferating, despite normal m DC numbers, reflecting a regenerative response that compensated for m DC loss. Blood m DC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of m DC in blood but resulted in accumulation of immature m DC in lymph nodes. Following SIV infection, lymph node m DC had an increased capacity to secrete tumour necrosis factor- α upon engagement with a Toll-like receptor 7/8 ligand that mimics exposure to viral RNA, and this was inversely correlated with MHC class II and CCR7 expression. Lymph node m DC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased m DC turnover, leading to accumulation in lymph nodes of immature m DC with an increased responsiveness to virus stimulation. [ABSTRACT FROM AUTHOR]

Invariant NKT (iNKT) cells are a distinctive subtype of CD1d-restricted T cells involved in regulating autoimmunity and capable of producing various T helper type 1 (Th1), Th2 and Th17 cytokines. Activation of iNKT cells by their exogenous ligand α-galactosylceramide (α-GalCer) exerts therapeutic effects in autoimmune diseases such as rheumatoid arthritis (RA). However, the pathophysiological role of iNKT cells in RA, in the absence of exogenous stimulation, is incompletely understood. We investigated the potential pathophysiological effects of iNKT cells in mice with collagen-induced arthritis (CIA), a model of RA. We found that iNKT cells underwent activation only in the early phases of the disease (6 days post-induction). In the liver, but not the spleen or lymph nodes, this early activation led to the release of interleukins -4, -17A and -10 and of interferon-γ; and an increased CD69 expression. Importantly, clinical and histological signs of arthritis were improved by the functional blockade of iNKT cells by a monoclonal antibody to CD1d at the early phase of the disease. This improvement was associated on day 6 post-induction with decreased expression of co-stimulatory molecules (CD80, CD86, CD40) on splenic dendritic cells and macrophages, whereas regulatory T-cell suppressive effects and proportions were not modified. Taken in concert, these findings suggest that iNKT cells are activated early in the course of CIA and contribute to the pathogenesis of arthritis. Therefore, iNKT-cell activation may be a valid treatment target in RA. [ABSTRACT FROM AUTHOR]

Chemokine receptor switching on lymphoid cells is an important factor regulating migration and homing, but little is known about the expression of such molecules during Mycobacterium tuberculosis infection in humans. We describe CCR2, CCR5 and CCR7 expression on human cells from blood, spleen and pulmonary hilar lymph nodes (PHLN) stimulated by M. tuberculosis antigens. CCR2 was not expressed by CD3+ cells regardless of the presence of antigen, but was highly expressed on CD14+ CD63+ monocytes/macrophages. CCR2 decreased on splenic monocytes/macrophages by nearly 50% in culture, independent of antigen, but remained high in blood and PHLN. CCR5 was low in CD3+ cells and was down-regulated by M. tuberculosis antigens on blood and splenic cells but not in PHLN. CCR5 was highly expressed on monocytes/macrophages and was down-regulated by M. tuberculosis antigens at 48 hr only in blood. Less than 15% of CD3+ cells from spleen and PHLN were CCR7+, whereas nearly 40% from blood expressed this receptor on primary isolation. However, CCR7 in PHLN increased in culture, independent of antigen. Monocytes/macrophages did not express CCR7. Thus, we characterize, for the first time, chemokine receptor expression and differential modulation by M. tuberculosis antigens on human mononuclear cells from spleen, blood and PHLN. Knowledge of chemokine receptor switching in human lymphoid tissue provides novel insight into mechanisms of the immune response to M. tuberculosis with potential effects on directing cell trafficking. [ABSTRACT FROM AUTHOR]

Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11·10 mice were less dependent on transforming growth factor (TGF)-β for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens. [ABSTRACT FROM AUTHOR]

The mouse Nrampl (Bcg) gene on chromosome 1 exerts pleiotropk effects on macrophage function. The gene is known to affect presentation of mycobacteria, and other antigens in vitro, so that macrophages carrying the resistant Bcg allele better support the proliferation of antigen-specific T cells compared with macrophages of the sensitive phenotype. To determine whether the Bcg allele could affect in vivo the antibody response to antigens not related to mycobacterial infections, we tested the primary and secondary responses to sheep red blood cells (SRBC) and glycosylated bovine insulin (G-insulin) in two pairs of Bcg congenic strains: BALB/c (Bcgs) versus BALB/c.CD2 (Bcgr), and B10.A (Bcgs) versus B10Ar (Bcgr), and in C57BL/10ScSn (B10; Bcgs) and A/J (Bcgr) mict. Furthermore, the antigen-specific proliferative responses of T cells primed in vivo by protein antigens were also tested in Bcg congenic mice. We found no significant difference in vim antibody response either to SRBC or G-insulin between the Bcgr and Bcgs strains. The magnitude of in vitro antigen-specific proliferation of lymph node cells sensitized in vivo by hen egg lysozyme (HEL) or chicken ovalbumin (OVA) was also similar in Bcgs and Bcgr congenic mice. However, we have documented a higher antigen-presenting capacity of Bcgr macrophages in vitro antigen-specific proliferation to OVA. Since the macrophages are the only cells in which the Nrampl gene is expressed, we suggest that the activity of other types of antigen-presenting cells masks the effect of the Bcgr allele on antigen-presentation in vivo. [ABSTRACT FROM AUTHOR]

We compared the capacity of mature dendritic cells (DC) from lymph nodes and maturing DC from spleens in their capacity to stimulate responses to the small hapten picryl sulphonic acid (PIC) and to the same hapten conjugated to ovalbumin (PIC-OVA) and requiring processing. Surface expression of major histocompatibility complex (MHC) class II molecules, which are upregulated during maturation of splenic DC, were studied as an independent marker of maturation. Freshly isolated lymph node DC had a veiled appearance and high levels of class II expression. DC separated from suspensions of spleen cells expressed the DC-specific marker NLDC-145, but were small, had low levels of MHC class II molecules and expressed stem cell antigen. Those DC from spleen cells cultured for 24 and 48 hr showed the development of typical veiled DC morphology and high class II expression. Lymph node DC stimulated high levels of primary T-cell proliferation to PIC, but failed to stimulate primary responses to PIC-OVA. Splenic DC isolated immediately failed to stimulate primary responses to either antigen. More mature spleen DC stimulated responses both to PIC and PIC-OVA. Surprisingly, development of the capacity to stimulate responses to PIC preceded that of stimulating PIC-OVA responses. The capacity of the DC to process and present PIC-OVA was maintained during the culture period. The results indicate that both the form of the antigen and the source and maturity of the DC are critical in determining the responses stimulated in T lymphocytes. [ABSTRACT FROM AUTHOR]

Tissue-specific circulation of T cells is a critical element in the integration of systemic immune responses. Current models of T-cell migration suggest that homing specificities oft cells for tissues such as gut and skin are generated outside the thymus as a result of activation of virgin T cells by antigen in lymph nodes. We have used the sheep fetus (which is immunologically virgin and contains no memory or effector T-cell subsets) to examine the migration of 51Crk-labelled T cells in vivo. We report that gut-homing T cells are not present in the fetus and that gut-homing T cells from postnatal lambs home normally to fetal gut. Fetal thymectomy performed immediately prior to birth failed to prevent the development of gut-homing T cells in postnatal life. Gut-homing specificities on T cells are thus acquired extrathymically. [ABSTRACT FROM AUTHOR]

During the induction phase of contact sensitization and other cutaneous immune responses a proportion of epidermal Langerhans cells (LC) is induced to leave the skin and migrate via afferent lymphatics to lymph nodes draining the site of exposure. The cells that accumulate in draining nodes have acquired the characteristics of immunostimulatory dendritic cells and effectively present antigen to responsive T lymphocytes. in the present study we have questioned whether LC in the epidermis and the lymph node dendritic cells into which they develop express interleukin-6 (IL-6), a cytokine that has been shown to serve as an important costimulator of T lymphocyte activation. In situ immunocytochemical analyses using a biotin-streptavidin staining technique revealed that dendritic cells resident in the epidermis of untreated mice constitutively express this cytokine. Keratinocytes expressed detectable IL-6 only following local exposure to the contact allergen oxazolone. Such treatment also appeared to enhance the expression by epidermal dendritic cells of this cytokine. Analyses of unfractionated and LC-enriched and -depleted populations of epidermal cells revealed a close correlation between major histocompatibility complex (MHC) class Il (la) antigen expression and staining for IL-6, implicating LC as the sole or major source of this cytokine in unstimulated epidermis. Finally, compared with tissue isolated from mice treated with vehicle alone, draining lymph nodes prepared from animals 18 hr following sensitization with oxazolone displayed a substantial increase in both the frequency of dendritic cells and the number of IL-6 cells within the paracortex. These data demonstrate that resident epidermal LC and the dendritic cells into which they develop are important sources of IL-6. Their constitutive and inducible expression of this cytokine will facilitate the induction of cutaneous immune responses. [ABSTRACT FROM AUTHOR]

The present study describes the distribution of CD4/CD8 double-positive (DP) T cells in lymph nodes and mucosa-associated lymphoid tissues of pigs at 6–7 months of age. Proportions of lymphocytes isolated from peripheral, bronchial and mesenteric lymph nodes expressing CD4 and/ or CD8 molecules were similar and ranged from 10-13% CD4/CD8 DP cells, 25-27% CD4 single-positive (SP) cells, and 27-32% CD8 SP cells. Mucosa-associated lymphoid tissues had significantly smaller proportions of CD4+ and/or CD8+ T cells than lymph nodes and CD4/CD8 DP cells accounted for a larger proportion of the total CD4+ lymphocytes than in lymph nodes. Compared to the lymph nodes, the predominant CD4+ and/or CD8+ T-cell subset in tonsils was the CD4/CD8 DP population (18%), because of both a higher proportion of these cells and a lower proportion of CD4 SP (12%) and CD8 SP (14%) lymphocyte subsets. Jejunal Peyer's patches were comprised of 12% CD4 SP, 28% CD8 SP and 10% CD4/CD8 DP lymphocytes. In contrast, the mid-section of the continuous Peyer's patch in the ileum contained 7% CD4 SP, 8% CD8 SP and 4% CD4/CD8 DP lymphocytes. The distribution of T lymphocytes in porcine mucosal lymphoid aggregates agrees with the reported correlation between high and low rates of lymphocyte entry into these tissues and the abundance or scarcity of T cells, respectively. Defining the role of CD4/CD8 DP lymphocytes and their unique distribution in mucosa-associated lymphoid tissues in the pig may reveal novel T-cell-mediated regulatory pathways. [ABSTRACT FROM AUTHOR]

A less virulent parasite of Plasmodium berghei K173 was isolated that induced immunity against the more virulent parasite. Immunity to this parasite but not to the virulent one, could be transferred by immune spleen cells but not by immune lymph node cells. However, the immune spleen cells did transfer immunity to the virulent strain if accompanied by infection with viable parasites of the less virulent strain, but only if they were allowed to proliferate for a period of I week before challenge with the virulent strain. Immune spleen cells could survive two cycles of mouse to mouse transfer. The induction of immunity by transfer of immune spleen cells was associated with the production of anti-parasitic antibody. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) acquire antigens in peripheral tissues, transport them to lymph nodes and present peptides to T cells. DC are particularly good activators of resting T cells. Murine Langerhans' cells (LC) are efficient at endocytosing and processing antigens but are very weak immunostimulators. In culture LC lose the ability to process antigen and become potent immunostimulators. Other peripheral DC are not well characterized and it is not known if they are similarly weak immunostimulators. We isolated DC from rat Peyer's patches (PP) and lamina propria (LP) of the small intestine, from intestinal lymph (LDC) and mesenteric lymph nodes, and examined their ability to stimulate an allogeneic mixed leucocyte reaction (MLR). Freshly isolated LP DC and PP DC could stimulate a moderate MLR but fresh LDC were significantly more potent. After overnight culture, LDC did not change their potency but DC from LP and PP became as potent as LDC. In contrast, fresh lymph node DC stimulated a MLR or oxidative mitogenesis as efficiently as LDC. These results show that the weak immunostimulation of murine LC is not characteristic of all peripheral DC. We compared the phenotypes of DC from different sites before and after culture. Different populations of DC show marked phenotypic heterogeneity in the expression of surface markers, particularly Thy-i, CD2 and the iC3b receptor. PP and LP DC were similar to MLN DC in their expression of markers, but differed from LDC. After culture there were marked changes in DC surface marker expression and the differences between the populations were reduced. These observations suggest that the heterogeneity observed in fresh populations does not signify different stages of maturation but may represent activation. [ABSTRACT FROM AUTHOR]

Following a single percutaneous vaccination with optimally irradiated cercariae of Schistosoma mansoni C57BL/6 mice mount a T-helper type-1 (Th1) lymphocyte-dominant immune response and are highly resistant to challenge infection. In this study, we show that, besides interferon-γ (IFN-γ), lymph node (LN) cells draining the site of vaccination produce significant amounts of interleukin (IL)-4 and IL-10 in culture with parasite antigen. After a challenge infection at the original site of vaccination, these LN cells did not generate an anamnestic Th1 response. Paradoxically, IFN-γ production and cell proliferation were profoundly down-regulated, whereas IL-4 production was enhanced and occurred earlier than in challenge control cultures. When challenge was applied to a site remote from vaccination, IFN-γ down-regulation was less evident, but the IL-4 response was consistently enhanced. Neutralization of IL-10 in vitro restored IFN-γ production by LN cells, whilst IL-4 levels were reduced. These data indicate that down-regulation of IFN-γ is controlled by IL-10 and/or IL-4. Mice showing down-regulated Th1 responses in the LN after S. mansoni challenge infection did not have a reduced ability to eliminate challenge parasites, indicating that the post-vaccination Th1 response had already armed the lungs with effector T cells before administration of challenge parasites. The observed phenomena of down- regulated Th1 and enhanced Th2 responses may be of relevance to other systems involving multiple infections or vaccination/boosting. Repeated applications to percutaneous sites having common lymphatic drainage would be expected to favour Th2 responses. Alternatively, in order to induce Th1-dominant responses and avoid unwanted IL-4/IL-10 induction, the use of remote sites is indicated. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) isolated from the lymph nodes or spleens of mice and pulsed with contact sensitizers or protein antigens stimulate primary proliferative responses by syngeneic T cells and responses to alloantigens in the mixed leucocyte reaction (MLR). Using enriched human peripheral blood DC, we attempted to stimulate primary immune responses to contact sensitizers by autologous lymphocytes/n vitro. No significant proliferation above background levels or CD69 expression (an early activation antigen on lymphocytes) was detected despite using a wide range of donors, chemicals, antigens and cell concentrations. Culture of DC for up to 5 days in vitro in the presence of phytohaemagglutinin (PHA)-conditioned culture supernatants, or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) also failed to induce primary proliferative responses to contact sensitizers. Comparisons were made between blood and lymph node DC from mice to explore whether the lack of stimulation was the result of differences between mouse and human DC or between DC isolated from different tissues. DC from lymph nodes stimulated primary responses to contact sensitizers in both blood and lymph node lymphocytes whereas blood DC did not stimulate responses. Both lymph node and blood DC stimulated an allogeneic MLR, although blood DC were less efficient than those from lymph node. The data show that DC from different tissues exhibit variable functional activity. DC from blood and lymph nodes were examined to determine whether surface antigen expression is related to functional activity. Murine blood DC expressed similar levels of LFA-1, LECAM-1 and CD44 compared with lymph node DC but lower levels of MHC class if, B7 and ICAM-1. These results may therefore have important implications for antigen processing and presentation in cells from different tissue compartments. [ABSTRACT FROM AUTHOR]

The T-cell repertoire to a prominent immunogen of Mycobacterium tuberculosis has been investigated on the assumption that differences in epitope specificity could influence the protective and pathogenic host reactions. Proliferative responses of lymph node and spleen cells to overlapping peptides, spanning the entire sequence of the 16,000 MW protein antigen were analysed in C57BL/10 and B10.BR mice. Following footpad priming and in vitro challenge with homologous peptide, 12 out of the 14 peptides tested were found to be immunogenic. However, only two peptides of residues 31-40 and 71-91 stimulated strong proliferative responses of T cells from mice which had been presensitized with either killed or live M. tuberculosis organisms; another three peptides were only weakly stimulatory. These epitopes have been immunodominant in both H-2b and H-2k mouse strains, indicating the genetically permissive nature of their recognition. Furthermore, both major immunodominant epitopes were found to be species specific for the M. tuberculosis complex and therefore potentially suitable for the early diagnosis of tuberculous infection. [ABSTRACT FROM AUTHOR]

L-selectin (LECAM-1, LAM-1) was expressed by a high proportion of CD4+ and CD8+ T cells, as well as almost all of the γδ T-cell receptor (TcR)+ (WC+) T cells, isolated from blood, lymph nodes or tonsils. CD4+ T cells in the lamina propria of the gut villi and CD8+ T cells in the villous epithelium as well as the majority of WC1+ T cells in the gut mucosa were L-selectin-. The proportion of T cells from Peyer's patches that synthesized the molecule was intermediate between the value for blood and gut mucosa. Expression of L-selectin therefore marks T cells in cattle with a distinct tissue distribution that correlates with its function as the peripheral node homing receptor. The proportion of CD4+ and CD8+ T cells in the circulation that were L-selectin+ decreased with age. Unlike CD45R, expression of L-selectin was not related to CD4 T-cell memory as judged by proliferation in transformation assays to soluble antigen. Three-colour immunofluorescent staining demonstrated four subpopulations of CD4 and CD8 T iymphocytes in peripheral blood mononuclear cells (PBMC) that were CD45R+, L-selectin+; CD45R+, L-selectin ; CD45R , L-selectin+; CD45R-, L-selectin-. CD44 memory cells were CD45R and L-selectin+ or L-selectin . Taken with earlier studies the reported observations demonstrated that only one of the four phenotypes of the CD4+ T cells in blood is present in the lamina propria of the gut villi and these are CD45R-, Lselectin-. Two of the four phenotypes of CD8+ T cells were present in the gut epithelium; these were CD45R+, L-selectin- or CD45R-, L-selectin. Expression of the bovine molecule was not rapidly down-regulated on T cells following activation by exposure to phorbol myristate acetate. [ABSTRACT FROM AUTHOR]

The distribution of bovine conglutinin (BK) in sections of frozen bovine tissues was studied by the indirect immunoperoxidase technique using a monospecific rabbit anti-BK antibody. BK was found in the cytoplasma of all hepatocytes, indicating that the liver is a major site of synthesis of BK. In the germinal centres of the spleen, tonsils and lymph nodes the anti-BK staining was restricted to a population of cells with a distribution and morphology characteristic of follicular dendritic cells. Macrophages in lung and thymus, and glia cells in cerebrum, revealed a granular staining reaction within the cytoplasma. Endothelial cells of blood vessels reacted with anti-BK. The intensity of this reaction varied greatly between the organs, the most pronounced reaction being seen in the glomeruli of the kidney, and in the capillary sinusoides of the cortex of the adrenal gland. The high endothelial venules of lymph nodes and tonsils were also stained. These findings suggest that BK, which until now has been described only as a circulating molecule, may exhibit a biological function within the BKpositive tissues. [ABSTRACT FROM AUTHOR]

We have examined immunological responses in the skin-draining lymph nodes (SLN) and lungs of mice during the 3 weeks after percutaneous exposure to attenuated larvae of Schistosoma inansoni. Cercariae irradiated with 20 krads (V20) were highly protective and sustained an increased number of CD4+ T cells in the SLN. On secondary exposure to schistosome antigen in vitro, these cells were capable of proliferating and secreting high levels of interferon-gamma (lFN-γ) and interleukin-3 (IL-3). However, in mice exposed to non-protective 80 krad-irradiated (V80) cercariae, secretion of these cytokines occurred early and only transiently. Significantly elevated numbers of CD4+ T lymphocytes were recoverable on Day 21 from the lungs of V20, but not V80 mice. These cells secreted high levels of IFN-&gamma and IL-3 in vitro, but not IL-2 and IL-4. Mice immunized intravenously with attenuated lung-stage schistosomula were not protected, despite having an elevated pulmonary lymphocyte population. Moreover these cells failed to secrete IFN-γ and IL-3. However, significant protection was achieved where exposure of mice to a combination of V80 cercariae and lung-stage schistosomula resulted in the recruitment of IFN-y secreting cells to the lungs. We conclude that the success of the irradiated vaccine depends not only on the generation of a population of antigen- specific T-helper cells in the SLN. but also recruitment of these cells to the lungs before challenge. [ABSTRACT FROM AUTHOR]

We have analysed the production of a wide variety of cytokines by in vitro concanavalin A (Con A) stimulated mesenteric lymph node cells (MLNC) from strains of mice experiencing chronic (B10.BR, AKR) venus acute (HALB/K) infection with the nematode parasite Trichuris muris. MLNC from infected BALB/K mice produced elevated levels of the Th2-specific cytokines interleukin-5 (IL-5) and IL-9. IL-3 and 11-4 remained at or just above normal. Interferon-gamma (IFN-γ) (a Th1-type cytokine) was secreted only in small amounts. MLNC from infected susceptible B10.BR and AKR mice produced large amounts of IFN-γ in the relative absence of IL-4 and IL-9. IL-5 levels failed to rise significantly above normal in H10.BR mice whilst in AKR mice high levels of IL-5 were detected early post-infection (p.i.) but levels decreased dramatically as the infection proceeded to reach normal levels by Day 34. IL-3 levels were depressed below normal. Our results are consistent with the polarization of the Th-cell response during T. muris infection to give predominantly IFN-γ-secreting Th1 cells in strains of mice unable to expel the parasite and mainly IL-4, 1L-5 and IL-9 producing Th2-type cells in resistant strains. [ABSTRACT FROM AUTHOR]

Non-major histocompatibility complex (MHC) restricted cytotoxicity is an important part of the immune reaction mounted in response to bovine herpes virus type 1 (BHV-1) infection. In this study, we evaluated the effect of BHV-1 infection on the ability of lung parenchyma leucocytes (LPL), cranial tracheobronchial lymph node cells (BLNC) and peripheral blood mononuclear leucocytes (PBML) to mediate this function. While LPL from non-infected calves mediated cytotoxicity against BHV-1-infected cells, a similar activity could not be detected in PBML or BLNC. in contrast, both LPL and PBML from naive calves could mediate cytotoxicity against K562 target cells but only after activation with interleukin-2 (IL-2). BLNC were unable to kill K562 cells. Infection of calves with BHV-1 enhanced the ability of LPL and PBML to kill BHV-1-infected cells. This enhancement was detected as early as Day 1 after infection in LPL whereas it could only be detected in PBML 8 days after infection. The results demonstrate that the leucocyte population present at the site of infection was able to mediate a potentially important antiviral function and that this function was enhanced rapidly in response to infection. Thus LPL-mediated cytotoxicity may be an important mechanism for the recovery from BHV-1 infection. [ABSTRACT FROM AUTHOR]

In flow microfluorometry analysis of thymus and lymph node cells of C57BL/6(I-E-,Mlsb) mice rendered neonatally tolerant to (C57BL/6 × AKR/J)F1 (I-E+,Mlsb/a) lymphoid cells, both CD4+ and CD8+ cells showed a striking reduction in the number of Vβ6+ cells capable of recognizing Mlsa in the context of major histocompatibility complex (MHC) class II molecules, indicating that clonal deletion of Vβ6+ cells by Mlsa antigen occurs just at a stage of immature Vβ6lowCD4+CD8+thymocytes. On the other hand, the number of Vβ11+ cells capable of recognizing I-E was markedly reduced in CD4+ cells, but CD8+ cells showed only partial (20%) reduction of such a population. The clonal deletion of Vβ11+ cells by I-E may begin at the transitional stage from Vβ11lowCD4+CD8+ to Vβ11highCD4+CD8- single-position cells, and Vβ11lowCD4+CD8+ cells differentiating to Vβ11highCD4-CD8+ cells seem to be resistant to clonal deletion. Vβ11+ T cells are also stimulated by staphylococcal enterotoxin A (SEA) irrespective of expression of CD4 or CD8. Nearly all of both Vβ11+CD4+ and Vβ11+CD8+ lymph node T cells were deleted by the injection of SEA every other day from birth. In their thymi, both Vβ11+CD4+CD8- and Vβ11+CD4 CD8+ single-positive thymocytes were deleted, and the proportion of Vβ11low thymocytes was lower than that of normal mice. The clonal deletion of Vβ11+ T cells by SEA injection occurs at a stage of immature Vβ11lowCD4+CD8+ double-positive thymocytes, resulting in deletion of both Vβ11+CD4+ and Vβ11+CD8+ T cells. [ABSTRACT FROM AUTHOR]

Biologically active interleukin-1(IL-1) has been detected in supernatants of draining lymph node cells isolated from contact-sensitized mice. Induction of IL-1 was dependent upon the concentration of sensitizer applied and occurred within 2 hr of exposure. The IL-1 activity could not be attributed to other interleukins and was neutralized by a specific antiserum. Reduced concentrations of IL-1 were produced by cells isolated from the draining nodes of mice that had been pre-exposed to the sensitizer. Since IL-1 has the potential to influence several aspects of lymphocyte activation, the production of significant concentrations of biologically active IL-1 by draining lymph node cells indicates that it is likely to play an important role in the afferent phase of contact sensitization. [ABSTRACT FROM AUTHOR]

By using a series of overlapping synthetic peptides that cover more than 75% of the amino acid sequence of the major surface glycoprotein (gp63) from Leishmania major, 11 T-cell epitopes in CBA and BALB/c mice have been identified. Six of the peptides were recognized by T cells of CBA mice recovered from L. major infection, while one was recognized by the T cells from BALB/c mice recovered from the infection following sublethal doses of gamma-irradiation. Lymph node cells from mice immunized with the peptides also responded to a number of the same peptides (seven in CBA and one in BALB/c). Peptide p10-28 induced proliferative T-cell responses in both CBA and BALB/c mice. Five of the peptides (p10-28, p22-40, p289-309, p459471 and p467-482) induced vigorous T-cell response in CBA mice but were not recognized by T cells from recovered mice. Four other peptides (p321-336, p364-476, p372-385 and p378-396) were recognized by T cells from recovered CBA mice but could not induce a T-cell response in normal CBA mice. Three peptides (p146-171, p289-309 and p395-414) were both able to induce a T-cell response and were recognized by T cells from recovered mice. However, only two peptides (p146-171 and p467-482) were able to activate T cells, which also recognized epitopes expressed by antigen-presenting cells infected with promastigotes. T cells induced by p146-171 and p467-171 or a mixture of these two peptides were mainly CD4+ and produced interleukin (IL-2) and interferon-gamma (IFN-γ) but not IL-4 upon antigen stimulation in vitro. These two peptides also induced a classical delayed type hypersensitivity (DTH) response in CBA mice, Furthermore, CBA mice immunized with a mixture of the two peptides in Coryne parvum or entrapped in liposomes induced significant resistance against L. major infection. The implications of these results in terms of a synthetic vaccine against leishmaniasis and the mechanism of the induction of Th1 and Th2 cells are discussed. [ABSTRACT FROM AUTHOR]

The effects of antigenic stimulation on the expansion of T-cell dependent areas in lymph nodes of mice were studied in relation to the effects on high endothelial venules (HEV) located in this area. Lymph nodes regional to areas of skin that had been treated with solutions of oxazolone were studied at several time-points after stimulation. The following measurements were made relative to lymph nodes of untreated animals: (i) the expansion of the T-cell dependent area in combination with the increase of HEV in this area, as detected by the HEV-specific mAb MECA-325, using morphometric analysis; (ii) the influx of FITC-labelled lymphocytes from the blood into the lymph node by FACS; (iii) the capacity of HEV to bind lymphocytes using an in vitro binding assay. Morphometry showed that T-cell dependent areas increased rapidly after stimulation with oxazolone and although the mean area of MECA-325-positive HEV had also increased, this increase lagged behind the expansion of the T-cell area. Therefore the amount of HEV per T-cell area in an antigen-stimulated lymph node was smaller than in an untreated lymph node and correlated with the percentage of FITC-labelled cells that had entered it. In a lymph node from an oxazolone-treated animal this percentage was decreased to the same order of magnitude as the area of HEV per T-cell area, but the overall binding capacity of HEV was not affected by oxazolone treatment. Antigenic stimulation therefore leads to a rapid expansion of the potential sites of lymphocyte entry into a lymph node, but the efficiency of the HEV does not change. [ABSTRACT FROM AUTHOR]