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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-10 has previously been shown to inhibit cytokine production by Th1 cells by blocking macrophage accessory cell function. In this study we demonstrate that dendritic cell-induced Th1 proliferation was unaffected by IL-10, whereas macrophage-stimulated proliferation was inhibited in the same system. In contrast dendritic cell induced IFN-gamma production by the Th1 clones was down-regulated by IL-10. Inasmuch as dendritic cells have been shown to be potent APC for T cells in primary responses we determined the effect of IL-10 on dendritic cell-induced proliferation and IFN-gamma production by CD4+ and CD8+ T cells. Dendritic cells were effective at stimulating both proliferation and IFN-gamma secretion of CD4+ or CD8+ T cells in a primary allogeneic mixed leukocyte response. In contrast, IL-10 markedly inhibited dendritic cell driven IFN-gamma production by purified CD4+ and CD8+ T cells. Down-regulation of dendritic cell-induced IFN-gamma production suggests a role for IL-10 in inhibiting the initiation of cell-mediated immune responses.
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PMID:Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production. 809 24

We isolated CD4+ and CD8+ T cell clones from pancreatic islets of non-obese diabetic (NOD) mice and studied their interactions with pancreatic islets, in culture. The three CD4+ T cell clones proliferated when cultured with islet cells from NOD, BALB/c, or C57BL/6 (B6) mice. For proliferation to the allogeneic islets, however, APC from NOD mice were required in the culture. Two of the clones also produced IFN-gamma upon culture with NOD islet cells. The Ag from islet cells responsible for T cell stimulation were not released into the supernatant but were cell associated. Paraformaldehyde treatment of islet cells, in fact, preserved their antigenicity. The fixed islet cells could present Ag to CD4+ T cell clones, provided live, syngeneic APC were added to the culture. We conclude from these experiments that islet cells donate Ag to the APC for presentation and that the function of APC is to process the Ag. The two CD8+ T cell clones proliferated and released IFN-gamma upon reaction with islet cells from either NOD or BALB/c but not B6 mice. The CD8+ T cell clones also reacted with the insulinoma NIT-1 cell line, derived from NOD mice. Fixation of NIT-1 cells did not impair recognition when live APC were present in the culture. In this case, however, the APC could be allogeneic. We conclude that CD8+ T cells directly recognized a MHC class I-restricted Ag on target cells, but needed the costimulatory effect of APC. We also found that CD8+ T cells killed islet cells. Two of the CD4+ T cell clones produced diabetes when transferred into male, irradiated NOD mice. For optimal transfer of disease, the CD4+ T cell clones had to be co-injected with CD8+ T cells from NOD diabetic mice. The two CD8+ T cell clones did not transfer disease.
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PMID:Presentation of beta-cell antigens to CD4+ and CD8+ T cells of non-obese diabetic mice. 810 46

IL-10 is a product of activated keratinocytes and is released during the induction phase of contact sensitivity. As IL-10 effects have been described as being mediated by APC, we investigated effects of IL-10 on epidermal Langerhans cells (LC), the resident APC in the epidermis. Initial studies failed to demonstrate effects of IL-10 on MHC class II Ag expression by LC or anti-CD3 mAb- or alloantigen-induced LC-dependent T cell proliferation. However, production of IFN-gamma and IL-2, (but not IL-6) was markedly reduced in these assays. When the soluble-protein Ag specific T cell clones AE7 (Th1) and D10.G4 (Th2) were substituted for unprimed T cells, differential effects of IL-10 on T-cell proliferation were observed. Whereas IL-10-pretreated and untreated LC supported Th2 cell proliferation equally well, IL-10-pretreated LC were essentially unable to induce Th1 cell proliferation in response to native protein or peptide Ag. The inhibitory influence of IL-10 on Th1 cells was observed when fresh or 1 day cultured LC were used; 2- or 3-day cultured LC were affected to a much lesser extent by IL-10 pretreatment. Further, coculture experiments using IL-10-pretreated or untreated LC of a different haplotype suggest that IL-10 negatively regulates a costimulatory signal required for induction of Th1 cell proliferation. To assess whether T cells incubated with Ag and IL-10-pretreated LC were responsive to further stimulation, T cells were rescued after 1 day of coculture with IL-10-pretreated LC and restimulated, either immediately or after 1 to 5 days of rest, with untreated LC in the presence of Ag. T cells incubated with IL-10-pretreated LC were found to be anergic, whereas T cells incubated with untreated LC proliferated normally after further stimulation. However, anergic T cells responded vigorously to IL-2. These data indicate that although IL-10-pretreated LC are effective APC for Th2 cells, they fail to induce Th1 cell proliferation and rather induce clonal anergy in these cells.
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PMID:Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. 810 65

The murine T cell surface molecules Ly-6C and Thy-1 are genetically and structurally distinct, yet they share two interesting properties: both are attached to the plasma membrane through a glycophosphatidylinositol linkage, and some mAb reactive with these molecules can activate T cells. Although mAb for Ly-6C and Thy-1 appear to mimic the function of physiologic ligands, direct evidence for the existence of these putative ligands has not been presented. In this report, we describe CTL clones that use Ly-6C and Thy-1 as accessory molecules for activation of cytolysis and the production of IFN-gamma based on inhibition of these functions with mAb. These studies were facilitated by the derivation of a nonactivating hamster IgM mAb specific for Ly-6C. CTL clones that use Ly-6C and Thy-1 as accessory molecules include a subpopulation of the previously described CD8+ alloreactive CTL that are not inhibited by mAb reactive with CD8, a CD8+ TCR-alpha/beta+ T cell clone specific for HSV glycoprotein D, and a CD4-CD8- TCR-gamma/delta+ T cell clone specific for HSV glycoprotein I. The role of Ly-6C and Thy-1 in target cell recognition is to some degree tissue-specific with respect to the APC/target cell. A mAb specific for Ly-6C appears to inhibit activation by prevention of adhesion between the effector cells and the target cells. This is the most direct evidence to date of a functional ligand for Ly-6C.
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PMID:Accessory molecules involved in antigen-mediated cytolysis and lymphokine production by cytotoxic T lymphocyte subsets. I. Identification of functions for the T cell surface molecules Ly-6C and Thy-1. 810 17

Processing of proteins into immunogenic forms and their subsequent presentation to T cells are mediated by APC. Monocytes and macrophages have long been recognized as one of the APC types. However, little is known about whether functional heterogeneity in processing and presentation exist within the monocyte/macrophage population. Past difficulties in obtaining clonal representatives of these populations have limited investigations in this regard. The c-myc-containing retrovirus MRV, previously shown to immortalize murine macrophages, was used to generate a large panel of macrophage cell clones. Differences observed in cell surface antigen expression and morphology demonstrated phenotypic heterogeneity among these clones. Functional heterogeneity was also observed both before and after IFN-gamma and IL-4 stimulation. The clones differ in their capacity to present several nominal antigens to T cell hybridomas. When parallel variation in ability to present both a nominal antigen and a peptide representing the epitope for which a T cell hybridoma was specific was observed among the clones, this variation correlated with the levels of surface MHC class II antigen the clones expressed. In contrast, diversity in the ability to process and present certain nominal antigens among clones that all presented the corresponding antigenic peptide with similar efficiency did not appear to be due to differences in levels of surface MHC class II molecules. Our results suggest that the macrophage clones are heterogeneous in their ability to both process and present several antigens. The ability to obtain macrophage tissue culture cell lines displaying phenotypic and functional heterogeneity should allow insight into the impact of normal macrophage heterogeneity on the outcome of immune responses in vivo.
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PMID:Monoclonal c-myc transformed macrophage cell lines. I. Heterogeneity in ability to process and present antigen. 810 18

In hypovitaminosis A, Ab-mediated immunity is severely impaired. We reported that Trichinella spiralis infection stimulates a strong Th2 cell response in control mice but in vitamin A-deficient mice it stimulates a strong Th1 cell response. Here we investigated the immunobiologic mechanisms underlying this shift from a Th2- to a Th1-dominated response. A kinetic analysis showed that the Th1 cells developed first and IFN-gamma secretion predominated in deficient mice, whereas the Th2 cells developed later and IL-5 and IL-10 secretion predominated in control mice. The IFN-gamma-secreting cell frequencies were the same but cells from deficient mice secreted IFN-gamma sixfold faster than cells from control mice, and retinoic acid addition in vitro decreased that rate 50%. In contrast, the IL-5-secretion rates were the same but the IL-5-secreting cell frequency was lower in deficient mice than in controls, and retinoic acid addition in vitro doubled this frequency independently of its inhibitory effect on IFN-gamma. The APC from deficient mice stimulated greater IFN-gamma release than control APC and retinoic acid addition in vitro decreased this activity 50%. Together these results identify at least three vitamin A activities that balance Th1 and Th2 functions, down-regulating Th1 cell IFN-gamma secretion directly, decreasing activated APC function, and promoting Th2 cell growth and/or differentiation. In this system and perhaps others, the imbalance between regulatory Th1 and Th2 cells is one mechanism underlying poor Ab-mediated immunity in hypovitaminosis A.
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PMID:In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function. 812 Mar 66

In the complete absence of APCs staphylococcal superantigens induced IL-2, IL-4, IL-5, IFN-gamma, and IL-2R gene transcripts in both highly purified human T cells and FACs sorted CD4+ memory (CD45RA-) T cells. Secretion of IL-2, IL-4, and IFN-gamma, as well as DNA synthesis, on the other hand, required the presence of monocytes. At cytokine gene transcript level, three patterns of expression were noted after superantigen activation of T cells in the presence vs the absence of APC. mRNA levels for IL-2 were markedly up-regulated in the presence of monocytes, IL-4 and IFN-gamma transcripts increased only modestly, and IL-5 and IL-2R mRNA levels were unaffected. Blocking mAbs against LFA-1 and LFA-3 added to staphylococcal enterotoxin B (SEB)-activated cultures of T cells and autologous monocytes, reproducibly decreased both T cell proliferation and genetic expression of IL-2, IL-4, IL-5, and IL-2R, although having little or no effect on IFN-gamma transcripts. Further, under those conditions of blocking, secretion of IL-2 and IL-4 was dramatically decreased, whereas IFN-gamma secretion remained essentially unchanged. In contrast, LFA-1 and LFA-3 mAbs completely abrogated IFN-gamma secretion from PHA-activated T cell-monocyte mixtures, although having no inhibitory effect on T cell proliferation. These results indicate a characteristic and differential involvement of adhesion molecule-mediated signals in superantigen-induced T cell proliferation, differential cytokine gene expression, and cytokine secretion.
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PMID:IL-2, IL-4, and IFN-gamma gene expression versus secretion in superantigen-activated T cells. Distinct requirement for costimulatory signals through adhesion molecules. 812 Mar 74

Cells of the macrophage lineage are required to cope with bacterial infection and to serve as APC for T lymphocytes. Among the regulatory factors limiting the macrophage response to infection and the expansion of Ag-specific T cells, IL-10 has received recent attention. On monocytes/macrophages, IL-10 has been shown to inhibit the intracellular killing of bacteria, the secretion of cytokines, and the expression of MHC molecules. In the present study we have examined the effect of IL-10 on different APC obtained from the central nervous system. Both, astrocytes and microglial cells are in a resting state and require activation signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly inhibits the IFN-gamma-induced expression of MHC class II Ag on microglial cells, it had no such effects on astrocytes. Nevertheless, IL-10 suppressed the MHC class II- and Ag-dependent proliferative response of T cells in the presence of both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced IL-10 influenced the function of microglia but not of astrocytes to serve as APC. IL-10 significantly inhibited the LPS-induced production of granulocyte-macrophage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial cells. In contrast, the secretion of these cytokines by the two glial cell population was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as stimuli.
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PMID:Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. 814 79

The role of costimulation in the activation of TCR-gamma delta cells in normal mice and mice transgenic (tg) for a TCR-gamma delta receptor was investigated. Activation of TCR-gamma delta cells required two signals. One signal was mediated by TCR occupancy, whereas a second signal was provided by accessory cells. The importance of the CD28/B7 interaction in the delivery of the second signal was demonstrated in multiple ways. First, addition of a soluble fusion protein homolog of CD28, CTLA4Ig, significantly inhibited the activation of G8 tg splenic TCR-gamma delta lymphocytes and intestinal epithelial TCR-gamma delta lymphocytes by Ag-bearing lymphocytes during primary stimulation. Similarly, both proliferation and IFN-gamma production were inhibited by addition of CTLA4Ig to secondary antigenic stimulation of G8 tg TCR-gamma delta cells. Second, an Ag-bearing thymoma, EL-4, was only able to stimulate expanded G8 tg TCR-gamma delta cells when the thymoma expressed B7. This stimulation was blocked by both CTLA4Ig and anti-B7 antibody. Third, antibodies to CD28 were able to mimic the costimulatory affect of APC. TCR-gamma delta cells cultured with either Ag-bearing fixed stimulator cells or submitogenic concentrations of immobilized anti-pan TCR-gamma delta mAb proliferated only in the presence of anti-CD28 mAb. Finally, G8 tg cells produced IL-2 only in the presence of APC costimulation or anti-CD28 antibodies, and the addition of exogenous rIL-2 overcame the need for costimulation. Thus, autocrine IL-2 production is one of the major consequences of TCR-gamma delta cell costimulation. Together these data demonstrate that costimulation is necessary for the activation of TCR-gamma delta cells and can occur through CD28 interaction.
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PMID:CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes. 824 49

Nonhybridized CD8+ Ts cell clones were generated from individual spleen cells of a B6D2F1 mouse, which had been immunosuppressed in an antigen-specific manner by administration of tolerogenic conjugates of ovalbumin (OVA) and monomethoxypolyethylene glycol. The cloned Ts cells were shown to suppress both in vivo and in vitro anti-OVA antibody formation in an antigen-specific and isotype-nonspecific manner, i.e., IgM, IgG1, and IgG2a anti-OVA antibodies were suppressed. The cytokine profile of three Ts cell clones was determined by bioassays, Western blot, and polymerase chain reaction analyses. It was shown that all the Ts cell clones produced IL-2, IL-4, IFN-gamma, TGF-beta 1, LT, and TNF-alpha upon activation with hamster anti-CD3 monoclonal antibody (mAb) or antigen plus APC. However, neither the mAbs to IFN-gamma, TGF-beta, or LT/TNF-alpha, nor the recombinant IL-2 was able to abrogate the suppression of in vitro antibody production by cloned Ts cells. These data are taken to indicate that (i) the cloned Ts cells suppress anti-OVA antibody production both in vivo and in vitro in an isotype-nonrestricted manner, (ii) the cytokine profile of these cloned Ts cells is similar to that of Th0 cells, and (iii) the immunosuppression mediated by these T cells is not directly related to the cytokines produced by cloned Ts cells.
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PMID:Cytokine gene expression of CD8+ suppressor T cells induced by tolerogenic conjugates of antigen and mPEG. 833 Mar 17


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