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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.

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]

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]

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.

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.

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.

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]

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]

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]

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]

An animal model was used to examine local and systemic cellular reactivity against virus infection of bowel mucosa. Firstly, existing techniques for extracting lymphoid cells from the dispersed populations of the bowel mucosa were adapted for use in rabbits and viable lymphocytes were isolated from the lapine ileal mucosa in numbers suitable for assay. Lamina propria lymphocytes (LPL) showed a strong blastogenic response to T-cell mitogens but intra-epithelial lymphocytes (JEL) responded poorly, even in the presence of splenic accessory cells. Next, chronically isolated deal loops in rabbits were infected with parainfluenzavirus type 3 (P1-3) and isolates from the organized and dispersed lymphoid tissues associated with infected ileal mucosac and those from systemic lymphoid sites were used in in vitro assays of virus-specific lympho-proliferation. A T-cell-mediated immune response against P1-3 was mounted in lymphoid tissues associated with the infected loops, appearing first in loop Peyer's patches (PP) at Day 4 and in mesenteric lymph nodes (MLN) and lamina propriae at Day 7 after infection. The response in PP had waned by 21 days but was sustained in the other sites for at least 42 days. Epithelial lymphocytes were consistently anergic and there was no evidence of specific reactivity at systemic lymphoid sites or elsewhere in the bowel. Thus, a highly localized T-cell-mediated response was sustained, not only in organized lymphoid tissues but also in the bowel wall itself, following infection with a novel antigen. [ABSTRACT FROM AUTHOR]

Congenic C57BL/6 mice (B6) homozygous only at the nu (nude, athymic) locus (B6 nu) or also at the lpr (lympho-proliferation) locus (B6 nu,lpr) were used as recipients for the transfer of spleen and/or lymph node cells from either normal B6 mice (B6+) or lpr-homozygous B6 mice (B6 lpr). Highly increased survival was obtained for [B6lpr → B6 nu,lpr] chimeras, but not for [B6+→B6 nu,lpr] and [B6 nu → B6 nu, lpr] chimeras. All long-term survivors that were killed showed an increased responsiveness to the T-cell mitogen concanavalin A (Con A) but no change of responsiveness to the B-cell mitogen lipopolysaccharide (LPS). Some enlargement of spleen and lymph nodes was observed only in some specific [B6 lpr → B6 nu,lpr] chimeras (female recipients of spleen cells). Within a few weeks after cell grafting, all but [B6 nu → B6 nu, lpr] chimeras developed highly increased levels of serum immunoglobulins, as well as a higher occurrence of anti-single-stranded (ss) DNA containing sera. These chimeras had been constructed in order to dissect the components of the lpr phenotype etiopathology (primordial involvement of B and/or T lineage cells, lymphoid and/or environmental influences). Though the evolution of serological parameters showed some chimera type-specific features, it seems difficult to reconstitute the entire expression of the lpr phenotype. [ABSTRACT FROM AUTHOR]

The mechanisms behind the induction of oral tolerance after feeding cholera toxin (CT) were examined using cell and serum transfer protocols. The feeding of CT or cholera toxoid (TD) induced a splenic cell capable of inhibiting the induction of systemic delayed-type hypersensitivity (DTH) but not humoral immunity. Depletion studies showed that this cell was Thy-1.2 positive. Transfer experiments suggested that suppressor cell activity was present in the mesenteric lymph nodes (MLN) and spleens of donor mice 1 week but not 3 days after feeding CT. When spleen cells were transferred to syngeneic recipients at various times after immunization, they were more effective at inhibiting systemic DTH when transferred within a short time of immunization. If the cells were transferred 6 days after immunization they no longer suppressed the development of DTH, which suggested that they inhibit the afferent limb of this immune response. This has been confirmed by the failure of a tolerogenic dose of CT, administered by gavage, to suppress the activity of mature effector TDTH cells. Serum collected 1 hr after feeding CT also suppressed the induction of systemic DTH. However, the tolerogenic activity of CT-fed serum was abrogated by the pretreatment of recipients with cyclophosphamide (Cy) (100 mg/kg), suggesting that this activity is mediated through the induction of suppressor cells. Transfer of fed serum, however, did not induce the splenic suppressor cell described above and we would suggest that several mechanisms may operate in the mucosal regulation of systemic DTH. [ABSTRACT FROM AUTHOR]

We have examined the role of donor natural killer (NK) cells in various forms of local and systemic graft-versus-host reaction (GvHR), by using beige mouse lymphocytes as the donor cell population. In contrast to lymphocytes from normal, congenic C57B1/6 (B6) mice, beige spleen cells could not induce either an acute, lethal GvHR or a proliferative form of GvHR in adult, unirradiated F1 hybrid hosts. In addition, beige donor cells produced little GvHR in the popliteal lymph node after local transfer and caused less severe and less sustained intestinal GvHR in unirradiated hosts. However, beige cells were fully capable of inducing a lethal GvHR in irradiated hosts. These studies indicate that beige mice have a defective ability to induce many types of GvHR, but suggest that this is a quantitative abnormality rather than an absolute lack of responsive cells. We propose that this may reflect a defect in T-cell function rather than a pure NK cell defect. [ABSTRACT FROM AUTHOR]

Mice were primed with TNP-derivatized insulin, or TNP-Mycobacteria, and lymph node cells were challenged in vitro with haptenated and unhaptenated antigens. Using either priming antigen, T-cell proliferative responses could be obtained to TNP-insulin. In B10 (H-2b), mice, which are responders to beef insulin (BI), but not to pork insulin (PI), TNP-BI or TNP-PI primed a response to TNP beef and TNP pork insulins, and to beef but not pork insulin, suggesting that a proportion of the response was directed to the modified portion of the molecule. However, priming with BI resulted in responsiveness to TNP-PI, but not to PI. Also, TNP-BI stimulated an augmented proliferative response in BI-primed mice. These results suggest that TNP modification can alter the antigenicity of the carrier molecule, perhaps by enhancing weak interactions with MHC molecules on presenting cells. Finally, there was no evidence that the TNP-dependent response to TNP-pork insulin was down-regulated by suppressor cells directed at the carrier molecule. [ABSTRACT FROM AUTHOR]

The number, distribution and surface phenotype of dividing cells in lymph nodes and blood and differences between the cell-cycle status of lymphocyte subpopulations were studied in lambs using double-labelling techniques. Dividing cells were labelled in vivo for various time periods with 5- bromo-2-deoxyuridine (BrdU). After removal of lymphoid tissues, the proportions of constituent lymphocyte subpopulations which had synthesized DNA during the labelling period were measured by flow cytometry or immunohistochemistry using a panel of monoclonal antibodies (mAbs) specific for sheep lymphocyte differentiation antigens and MHC class I and class II antigens in conjunction with an anti-BrdU mAb. There was a higher overall level of cell division in the ileocaecal lymph node than in either the prescapular or parathymic lymph nodes. In all three lymph nodes, the majority of lymphocytes which incorporated BrdU occurred in Ball follicles or germinal centers. CD4+ and CD8+ T cells had a higher level of cell division (LI 5-14%) than those recognized by mAb 197 (CD4 CD8- subset) (LI ≤3%). [ABSTRACT FROM AUTHOR]

The site and mechanism of recruitment of short-lived new B cells from the bone marrow into the longer-lived recirculating B-cell pool were studied by using kappa-allotype-distinct congenic rats to construct bone marrow chimeras. Chimeras were immunized with antigen in the form of an antigen- antibody complex that is largely restricted to lymphoid follicles, rapidly localizing to follicular dendritic cells (FDC). This form of antigen, although a potent stimulator of memory B cells, was shown to be a very poor inducer of virgin B-cell responses. This was not due solely to differences in receptor affinity, as complexes in which the hapten epitopes were unmasked also evoked little virgin B-cell response. The inability of virgin B cells to be activated by FDC-bound antigen seems to relate to the fact that they are not pan of the recirculating pool and do not migrate through lymphoid follicles; restriction of antigen to a draining lymph node also precluded virgin B-cell activation. The evidence presented suggests that activation of virgin B cells at extrafollicular sites in the spleen (red pulp, marginal zone, outer periarteriolar lymphocytic sheath) is required for both their incorporation into immune responses and into the recirculating pool. These experiments also show that established immune responses are maintained by clones activated soon after immunization and not by continued incorporation of new clones. [ABSTRACT FROM AUTHOR]

The relative proportions of CDS, CD4, CDL SBU-T 19 and surface immunoglobulin (sIg)-positive lymphocytes in normal sheep liven were determined by flow cytometry analysis of isolated liver leucocytes and compared to lymphocyte subpopulations found in peripheral blood and hepatic lymph nodes. In contrast to the blood, very low numbers of SBU-Tl9+ cells were found in both the liver and hepatic lymph nodes. The ratio of helper versus suppressor/cytotoxic T cells in the liver was less than 1, which was much lower than in blood or hepatic lymph nodes. A large proportion of liver Lymphocytes were characterized by a low intensity staining for the CD8 antigen (CD8L. Two-colour flow cytometry analysis revealed that the CD8L cells were negative for the CD5 pan Tall marker. It is suggested that these CD8LCD5 cells are natural killer (NK)cells similar to those found in the gut. An influx of CD8LCD5- cells was observed in leucocyte-infiltrated liver lesions at later stages of a rejection response to the cestode Taenia hydatigena. [ABSTRACT FROM AUTHOR]

Transfusion with donor blood before transplantation can prolong the survival of renal allografts in the rat. The phenomenon is donor specific. We have investigated the effect of blood transfusion on both lymphocyte proliferation and the generation of donor-specific cytotoxic cells. In the first instance the kinetics of the proliferative responses of lymph node, spleen and thoracic duct lymph (TDL) leucocytes (harvested 7 days after transfusion of donor-specific blood, third-party allogeneic blood, syngeneic blood or no treatment) to lymph node stimulator cells were determined in a one-way mixed lymphocyte culture (MLC). Four strain combinations (LEW to DA, LEW to PVG, PVG to DA and DA to PVG) were investigated in this study. Maximal proliferation was observed at 4 days in the MLC and this was not altered by prior blood transfusion. When lymph node and TDL cells from transfused recipients were used as responders and stimulation was provided by cells from the same strain of rat as the blood donor, there was a significant depression of the MLC response compared to the response of cells harvested from untreated animals or animals given a syngeneic blood transfusion. This correlated with the behaviour of renal allografts in the same strain combinations. Lymph node and TDL cells harvested from rats that had received a third-party blood transfusion produced variable results in the MLC, ranging from a normal to a depressed response. No prolongation of allograft survival was noted in any animals pretreated with third-party blood. In contrast, when spleen cells were used as responder cells there was a donor-specific increase in the proliferative response on Day 4 in all strain combinations tested. In the second instance, specific cytotoxic activity was generated by in vitro (MLC) stimulation of lymph node or TDL, but not spleen, cell responders harvested from transfused or untreated rats. The activity of cytotoxic cells generated in MLC was quantified in a 51Cr-release assay, using Con A blast lymph node target cells prepared from animals of the same strain as the blood donor or a third-party strain. The specific cytotoxic activity generated was significantly increased when the responding cells were harvested from an animal that had received a donor-specific transfusion and then been restimulated by the blood donor in M LC. Thus donor-specific transfusion results in a reduction in the proliferative response of lymph node and TDL cells to blood donor-specific stimulators in MLC; however, it would appear to prime the recipient against the histocompatibility antigens of the blood donor and results in the enhanced generation of donor-specific cytotoxic cells after restimulation in vitro. [ABSTRACT FROM AUTHOR]

To investigate the role of the NLDC-145 antigenic determinant on interdigitating cells in T-cell dependent areas of lymphoid organs, rosettes were isolated from interdigitating cells and lymphocytes from lymph nodes. By using allotypic mixtures it was established that these rosettes represented pre-existing associations of interdigitating cells and lymphocytes. Phenotypic analysis of the lymphocytes showed that most cells in these rosettes were T cells. After antigenic stimulation, an increase of helper T cells and of B cells associated with the rosettes was found. Incubation of the rosettes with the NLDC-145 antibody did not alter the composition of the rosettes. By neonatal injection of the NLDC-145 antibody, the influence of the antigen on T-cell differentiation and antigen presenting was investigated. Although the antibody could be detected easily on interdigitating cells and thymus cortex of injected animals, no direct influence of long-term injections of the antibody from birth on antigen presentation and T-cell differentiation was found. [ABSTRACT FROM AUTHOR]

Spleen and mesenteric lymph node cells from Nematospiroides dubius-infected and normal control mice were cultured in vitro with N. dubius antigen. Proliferation of these cells in response to antigen was measured by the uptake of [&3sup;H]TdR. Cells harvested from mice during a primary infection did not proliferate in vitro; however, low levels of specific proliferation could be demonstrated if these mice were treated on Day 5 post-infection with 20 mg/kg of cyclophosphamide i.p. A strong cell proliferative response was measured 6 days following a challenge infection; spleen cells responded more strongly than cells from the mesenteric lymph nodes (M LN), but the addition of lymph node cells to spleen cell cultures did not suppress the latter response. Responsiveness of spleen cells to concanavalin A (Con A) was two-fold higher in infected mice than in normal controls, but the proliferation of MLN cells to Con A was similar in infected and uninfected mice. When N. dubius- resistant B10.BR (H-2k) mice were compared to the susceptible B10.BR (H-2f) mice, no differences were observed in the spleen cell response to N. dubius adult antigen following challenge infections. However, after a tertiary infection, MLN cells from the resistant strain proliferated strongly in comparison to cells from susceptible mice. Spleen or MLN cells from resistant mice transferred immunity to naive recipients provided that the recipients had received a prior injection i.p. with adult N. dubius antigen. The injection alone, or cells in the absence of the injection, failed to protect the recipients from N. dubius challenge. [ABSTRACT FROM AUTHOR]

The development of T lymphocytes in ovine fetal lymph nodes was studied immunohistologically using a panel of monoclonal antibodies. T lymphocyte subsets appeared within the ovine fetal lymph node in a specific sequence. SBU-T1- and SBU-T8-positive lymphocytes were seen at Day 47 of gestation. LCA, sIg, MHC I, MHC II, SBU-T6 and 46.66 antigens were also seen within the lymph node at this time, The first SBU-T4-positive cells were seen within the fetal lymph node at Day 50 of gestation, along with the first 20.96-, 25,69- and 38,38-positive cells. SBU-TI9 lymphocytes appeared later in gestation, being present in fetal lymph nodes from Day 69 of gestation. The appearance and distribution of T and B cells in the developing lymph nodes of the ovine fetus is described and compared with the ontogeny of lymphocytes in the fetal thymus and spleen. [ABSTRACT FROM AUTHOR]

The effects on lymphokine production of two agents known to potentiate delayed-type hypersensitivity (DTH), pertussigen (pertussis toxin) (PT) and cyclophosphamide (CY) have been investigated. These two agents were administered to immunized mice. Subsequently, lymph nodes and spleen cells were exposed to specific antigen in vitro. The resulting culture supernatants were assayed for the presence of lymphokines. Only supernatants of cells from the mice given PT contained appreciable quantities of interferon-γ (IFN-γ) and stimulated cells of the monocyte-like WEHI-265 cell line to produce procoagulant activator and plasminogen activator. On the other hand, CY was more effective than PT on the production of interleukin-3 (IL-3). Both adjuvants had small enhancing effects on the production of interleukin-2 (IL-2). With either adjuvant, the cell populations induced had a similarly enhanced capacity to transfer DTH. These results demonstrate that the capacity of cells to transfer DTH does not necessarily correlate with their release of particular lymphokines. The potentiation of DTH by cyclophosphamide did not depend on significantly enhanced generation of IFN-γ, procoagulant activator, or plasminogen activator. The amount of IFN-γ in the culture supernatants correlated with their capacity to produce procoagulant activator and plasminogen activator, whereas the amount of IL-2 and IL-3 did not. [ABSTRACT FROM AUTHOR]

Antigen-specific T-helper cells for IgA responses arise in Peyer's patches (PP) following their immunization by subserosal injection of keyhole limpet haemocyanin (KLH). These are of the W3/25 phenotype and the W3/25 receptor is shown here to be involved in their helper function. These cells originate in PP and migrate via mesenteric lymph nodes (MLN) to thoracic duct lymph, although the MLN appear to be unnecessary for the induction or maturation of antigen-specific helper cells collected in thoracic duct lymph after intra-Peyer's patch (i.p.p.) immunization. KLH-specific helper cells can be detected subsequently in the intraepithelial lymphocyte population and also among lamina propria lymphocytes. The helper cells also relocate to PP distant to their site of origin where they are retained only when antigen is present. While i.p.p. immunization is an efficient route for the induction of IgA helper cells in gut-associated lymphoid tissue, it differs from oral immunization in that concomitant induction of antigen-specific splenic suppressor cells does not occur, indicating a role for epithelial antigen processing in this phenomenon. [ABSTRACT FROM AUTHOR]

DBA/1 mice develop systemic polyarthritis and high titres of collagen autoantibodies after immunization with type II collagen. In this study we have analysed the frequency and specificity of antibody-producing B cells in draining lymph nodes 11 days after a primary immunization with rat type II collagen. A remarkably high frequency of type II collagen-reactive hybridomas (30%, n = 71), the majority cross-reacting with autologous type II collagen, were generated. Most of the collagen-reactive hybridomas produced IgG antibodies specific for type II collagen. Many other hybridomas produced multispecific antibodies (9%): these were preferentially of the IgM class. Some of the monoclonal multispecific hybridomas produced antibodies that cross-reacted with specific epitopes on the collagen molecule. One type II collagen-reactive hybridoma also displayed rheumatoid factor activity. Different mechanisms for the generation of the high frequency of collagen reactive antibodies are discussed. [ABSTRACT FROM AUTHOR]

The immunosuppressive activity of serum from PVG rats following orthotopic transplantation of DA liver has been examined in vitro. Liver grafts in this combination are never rejected, but induce a state of specific transplantation tolerance in the recipient. Serum from such tolerant animals was able to inhibit proliferation of normal PVG lymph node cells in response to DA stimulators in the mixed lymphocyte reaction (MLR); inhibition was specific for donor (DA) antigens. Interleukin-2 (IL-2) production during the MLR was also reduced. The production of anti-DA cytotoxic T cells developing in the MLR was not affected, but the total yield of such cells was reduced. Evidence was obtained that part of the inhibitory serum activity was due to IgG antibody against class II RT1a alloantigens. Thus, a purified IgG fraction retained much of the inhibitory activity which could be removed by an anti-IgG absorbent. Studies of MLR inhibition in different rat strains indicated the anti-class II specificity of the inhibitory IgG. Lymph node cells from DA-liver-grafted PVG rats responded normally against DA stimulators in vitro, and this MLR was also blocked by the inhibitory IgG. Our results suggest that anti-class II allo-antibody may play a role in immunosuppression and long-term graft survival following liver transplantation in this combination. [ABSTRACT FROM AUTHOR]

Mesenteric lymphoblasts have a predilection to localize selectively in the murine small intestine within 24 hr after adoptive transfer. In this report, we quantify the localization and intraintestinal distribution of radiolabelled mesenteric lymph node (MLN) T and B blasts in relation to the in situ distribution of intestinal T and B cells which were detected immunohistochemically. Our results show that, within 24 hr after transfer, MLN T blasts localized predominantly in the intestinal epithelium and villus lamina propria, whereas B blasts were found mostly in the basal lamina propria of the gut. In the epithelium and villus lamina propria, 100% and 68%, respectively, of labelled were of thymic origin; this cell type comprised 54% of labelled cells in the basal lamina propria. This pattern of localization was the reverse of the distribution of T lymphocytes and B-cell derived plasmacytes residing in the intestinal wall. These results suggest that MLN T lymphocytes may be a component of common mucosal immunological system and may be integrated with peripheral immunity according to the immunological needs of the host. [ABSTRACT FROM AUTHOR]

Two mouse monoclonal cytotoxic antibodies (ST-Ia and ST-Ib) recognize an antigen present on the large majority of thymocytcs and all T cells in the periphery. but not B cells or other haemopoietic cells in sheep. Examination of frozen sections of various fetal tissues revealed that the cells expressing this antigen first appeared in the thymus, and these cells markedly increase in numbers in the peripheral lymphoid tissues after mid-gestation. Large accumulations of positive cells were located in the paracortex of lymph nodes, the periarteriolar lymphoid sheath of the spleen, and interfollicular areas of jejunal Peyer's patches. all of which are known to be T-dependent areas. Treatment of lymphocytes with ST-Ia and complement resulted in the abrogation of T-proliferative responses, but the response to a B-cell mitogen. lipopolysaccharidc. was not reduced. Neither ST-Ia, nor ST-Ib cross-reacted to lymphocytes obtained from other species of animals (man, monkey, mouse, rat, guinea. pig, chicken, frog, pig, horse, goat and cattle). Based on these findings, it was concluded that the expression of the antigen recognized by ST-Ia and ST-Ib is restricted to the T-cell lineage of sheep, and that all ovine I cells express this antigen. Furthermore, ST-Ia and ST-Ib were determined to recognize the same antigen by reciprocal blocking experiments. [ABSTRACT FROM AUTHOR]

Mice of the C57BL/10 (B 10) strain are slow responders to infection with T. spiralis in terms of ability to expel worms from the intestine. Compared with rapid-responder NIH mice, infection stimulates a slower and reduced blast cell response in the draining mesenteric lymph node (MLN). Transfer of immune cells from the MLN (MLNC) does not accelerate worm expulsion from naive B 10 recipient mice, even though MLNC from this strain effectively transfer immunity to (B10 × NIH) F1 recipients. In common with other B 10 background mice C57BL/10 show an infection-dose related suppression of immunity to T. spirolis. Such suppression does not appear to determine the response to MLNC, as adoptive transfer into 810 recipients was not enhanced by reducing the level of challenge infection given, and transfer into F1 recipients was unaffected by simultaneous transfer of lymphocyte populations from donors infected at a level which would induce suppression. A hypothesis is proposed which relates slow response status to (i) the inherent capacity of the intestinal inflammatory component of worm expulsion, and (ii) the outcome of infection-dose related stimulatory and suppressive influences acting on the two interacting lymphocyte components of expulsion. The relevance of H-2-linked and non-H-2 genes to the control of the response is discussed. [ABSTRACT FROM AUTHOR]