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

Murine T lymphocytes recognize nominal Ag presented by class I or class II MHC molecules. Most CD8+ T cells recognize Ag presented in the context of class I molecules, whereas most CD4+ cells recognize Ag associated with class II molecules. However, it has been shown that a proportion of T cells recognizing class I alloantigens express CD4 surface molecules. Furthermore, CD4+ T cells are sufficient for the rejection of H-2Kbm10 and H-2Kbm11 class I disparate skin grafts. It has been suggested that the CD4 component of an anti-class I response can be ascribed to T cells recognizing class I determinants in the context of class II MHC products. To examine the specificity and effector functions of class I-specific HTL, CD4+ T cells were stimulated with APC that differed from them at a class I locus. Specifically, a MLC was prepared involving an allogeneic difference only at the Ld region. CD4+ clones were derived by limiting dilution of bulk MLC cells. Two clones have been studied in detail. The CD4+ clone 46.2 produced IL-2, IL-3, and IFN-gamma when stimulated with anti-CD3 mAb, whereas the CD4+ clone 93.1 secreted IL-4 in addition to IL-2, IL-3, and IFN-gamma. Cloned 46.2 cells recognized H-2Ld directly, whereas recognition of Ld by 93.1 apparently was restricted by class II MHC molecules. Furthermore, cytolysis by both clones 46.2 and 93.1 was inhibited by the anti-CD4 mAb GK1.5. These results demonstrate that CD4+ T cells can respond to a class I difference and that a proportion of CD4+ T cells can recognize class I MHC determinants directly as well as in the context of class II MHC molecules.
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PMID:Some cloned murine CD4+ T cells recognize H-2Ld class I MHC determinants directly. Other cloned CD4+ T cells recognize H-2Ld class I MHC determinants in the context of class II MHC molecules. 171 78

Murine IL-10 (cytokine synthesis inhibitory factor) inhibits cytokine production by Th1 cell clones when they are activated under conditions requiring the presence of APC. By preincubating APC with IL-10, we demonstrate that IL-10 acts principally on APC to inhibit IFN-gamma production by Th1 clones. Moreover, IL-10 is not active when Th1 cells are stimulated with glutaraldehyde-fixed APC, which also indicates that its action involves regulation of APC function. Furthermore, IL-10 inhibits cytokine synthesis by Th1 cells stimulated with the super-antigen Staphylococcus enterotoxin B, which does not appear to require processing. Flow microfluorimetry purified splenic or peritoneal B cells and macrophages, and B cell and macrophage cell lines can present Ag to Th1 clones. However, IL-10 acts only on sorted macrophages and the macrophage cell line to suppress IFN-gamma production by Th1 clones. IL-10 does not show this effect when B cells are used as APC. In contrast, IL-10 does not impair the ability of APC to stimulate cytokine production by Th2 cells. IL-10 does not decrease IFN-gamma-induced I-Ad levels on a macrophage cell line. Inasmuch as IL-10 also inhibits IL-2-induced IFN-gamma production by Th1 cells in an Ag-free system requiring only the presence of accessory cells, these data suggest that IL-10 may inhibit macrophage accessory cell function which is independent of TCR-class II MHC interactions.
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PMID:IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. 182 84

The helper activity of resting T cells and in vitro generated effector T cells and the relative roles of cognate interaction, diffusible cytokines, and non-cognate T-B contact in B cell antibody responses were evaluated in a model in which normal murine CD4+ T cells (Th), activated with alloantigen-bearing APC, were used to support the growth and differentiation of unstimulated allogeneic B cells. Both "fresh" T cells, consisting of memory and naive cells, stimulated for 24 h, and "effector" T cells, derived from naive cells after 4 days of in vitro stimulation, induced the secretion of IgM, IgG3, IgG1, IgG2a, and IgA. Effector T cells were significantly better helpers of the response of small dense B cells, inducing Ig at lower numbers and inducing at optimal numbers 2- to 3-fold more Ig production than fresh T cells. The predominant isotype secreted was IgM. Supernatants derived from fresh T cell cultures contained moderate levels of IL-2, whereas those from effector cultures contained significant levels of IL-6 and IFN-gamma in addition to IL-2. The involvement of soluble factors in the B cell response was demonstrated by the ability of antibodies to the cytokines IL-2, IL-4, and IL-6 to each block Ig secretion. Antibodies to IL-5 and IFN-gamma had no effect on the T cell-induced response. Kinetic studies suggested that IL-4 acted during the initial stages of the response, whereas the inability of anti-IL-6 to block B cell proliferation suggested that IL-6 was involved in part in promoting differentiation of the B cells. The relative contributions of cognate (MHC-restricted) and bystander (MHC-unrestricted) T-B cell contact vs cytokine (non-contact)-mediated responses were assessed in a transwell culture system. The majority of the IgM, IgG3, IgG1, and IgG2a response induced by both fresh and effector T cells was dependent on cognate interaction with small, high density B cells. In contrast, a small proportion of these isotypes and most of the IgA secreted resulted from the action of IL-6 on large, presumably preactivated, B cells. The IgA response did not require cell contact or vary when fresh and effector cells were the helpers. The contribution of bystander contact in the overall antibody response to both T cell populations was minimal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:B cell response to fresh and effector T helper cells. Role of cognate T-B interaction and the cytokines IL-2, IL-4, and IL-6. 182 58

IL-10 inhibits the ability of macrophage but not B cell APC to stimulate cytokine synthesis by Th1 T cell clones. In this study we have examined the direct effects of IL-10 on both macrophage cell lines and normal peritoneal macrophages. LPS (or LPS and IFN-gamma)-induced production of IL-1, IL-6, and TNF-alpha proteins was significantly inhibited by IL-10 in two macrophage cell lines. Furthermore, IL-10 appears to be a more potent inhibitor of monokine synthesis than IL-4 when added at similar concentrations. LPS or LPS- and IFN-gamma-induced expression of IL-1 alpha, IL-6, or TNF-alpha mRNA was also inhibited by IL-10 as shown by semiquantitative polymerase chain reaction or Northern blot analysis. Inhibition of LPS-induced IL-6 secretion by IL-10 was less marked in FACS-purified peritoneal macrophages than in the macrophage cell lines. However, IL-6 production by peritoneal macrophages was enhanced by addition of anti-IL-10 antibodies, implying the presence in these cultures of endogenous IL-10, which results in an intrinsic reduction of monokine synthesis after LPS activation. Consistent with this proposal, LPS-stimulated peritoneal macrophages were shown to directly produce IL-10 detectable by ELISA. Furthermore, IFN-gamma was found to enhance IL-6 production by LPS-stimulated peritoneal macrophages, and this could be explained by its suppression of IL-10 production by this same population of cells. In addition to its effects on monokine synthesis, IL-10 also induces a significant change in morphology in IFN-gamma-stimulated peritoneal macrophages. The potent action of IL-10 on the macrophage, particularly at the level of monokine production, supports an important role for this cytokine not only in the regulation of T cell responses but also in acute inflammatory responses.
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PMID:IL-10 inhibits cytokine production by activated macrophages. 194 Mar 69

To further the understanding of the role of T cells in immunity to the parasite Toxoplasma gondii, antigen-specific T cell clones were generated using peripheral blood mononuclear cells from seropositive individuals. Whole parasites were used to stimulate a proliferative expansion of antigen-reactive cells, followed by limiting dilution cloning in the presence of irradiated, autologous PBMC and rIL-2. Three parasite antigen-specific T cell clones expressing the CD3+ phenotype were selected for further characterization. Phenotypic analysis with monoclonal antibodies revealed two clones reactive with CD8 (RTg1 and RTg3) while the other (RTg2) phenotyped as CD4+, CD8-. When tested in a proliferation assay using a panel of different T. gondii proteins, clone RTg1 reacted with a single large protein (Mr greater than 180,000) as well as smaller components (less than 12,000), clone RTg2 reacted with a protein of Mr = 28,000 and clone RTg3 reacted with a protein of 116,000 plus smaller components (less than 12,000). Only the 28,000 = Mr antigen recognized by RTg2 was reactive on Western blot with autologous donor antisera. All three clones produced IFN-gamma and IL-2 in varying amounts upon antigenic stimulation in the presence of irradiated APC. Moreover, one clone RTg1, exhibited direct parasite cytotoxicity, inhibiting extracellular T. gondii by greater than 70% when incubated at an effector/target ratio of 40:1. This clone was alpha, beta TCR heterodimer positive and exerted its cytotoxic parasiticidal activity in the apparent absence of MHC restriction. The results provide evidence for the existence of circulating antigen-specific cytotoxic T cells in normal humans who are toxoplasma antibody seropositive.
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PMID:Induction of antigen-specific human cytotoxic T cells by Toxoplasma gondii. 197 29

Lymphokine secretion profiles were studied of human allergen-specific CD4+ T lymphocyte clones (TLC). To this aim, panels of house dust mite Dermatophagoides pteronyssinus (Dp)-specific TLC were generated from two atopic Dp-allergic patients, suffering from severe atopic dermatitis (AD1) and allergic asthma (AD2), respectively, and from a non-atopic individual (NAD). From AD1 additional TLC were cloned specific for tetanus toxoid or Candida albicans, both Ag that were not relevant for the atopic state of this patient. Secretion of IL-2, IL-4, and IFN-gamma was determined after specific stimulation of these TLC, using autologous monocytes as APC. With respect to the production of IL-4 and IFN-gamma, clearly distinct profiles were observed. All Dp-specific TLC from both atopic donors produced IL-4 but not IFN-gamma, whereas the Dp-specific TLC from NAD, as well as the tetanus toxoid- and C. albicans-specific TLC from AD1, all produced IFN-gamma but not or small quantities of IL-4. Most TLC from all panels produced IL-2. These lymphokine profiles were consistent for at least 3 days and were neither dependent on the dose of allergen nor on the atopic or nonatopic state of the donor of APC. The functional consequence of these restricted lymphokine profiles was stressed by the observation that, whereas Dp-specific TLC from AD1 and AD2 supported in vitro IgE production, this support could be abrogated by a Dp-specific TLC from NAD. The present results suggest that CD4+ T lymphocytes that produce IL-4, but not IFN-gamma, occur in high frequencies in the allergen-specific T cell repertoires of atopic donors, which may have important implications for the pathomechanism of atopic disease.
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PMID:Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. 197 64

Delayed type hypersensitivity reaction (DTH) consists of a sequential cascade of steps depending on different types of T cells, as well as mast cells, endothelial cells and macrophages. Recently it has been shown that CD4+ TH1 lymphocytes ("inflammatory type") play a central role in DTH reaction. Activated TH1 cells produce a characteristic pattern of cytokines: IL-2, IL-3, TNF-beta, IFN-gamma. Using the contact sensitivity (CS) reaction on mice as a model system, the role of cytokines in the regulation of DTH is presented, particularly the significance of IL-3 and IL-6. The recent data can be interpreted to show that IL-6 released by activated macrophages (APC cells) in the induction phase of the CS reaction probably stimulate CD8+ T suppressor cells. These in turn inhibit the production of IL-2 and IL-3 by CD4+ TH1 cells followed by a state of unresponsiveness.
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PMID:Cell-mediated immunity: role of IL-3 and IL-6 in the regulation of contact sensitivity reaction. 209 80

Fixation of APC with 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide (ECDI) eliminates their ability to stimulate proliferation of alloreactive T cells or the D10 T cell clone, although a partial response, IL-4 production, was measured. However, if APC were activated before fixation, they could be ECDI-fixed and retain the ability to induce T cell proliferation. IL-1, IL-4 or LPS were capable of activating APC in this way, whereas IFN-gamma was not. This activation step occurred in 6 h, required protein synthesis, and was distinct from increases in Ia or IL-1. This suggests resting APC lack structures that are essential for inducing T cell proliferation.
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PMID:A role for cytokines in antigen presentation: IL-1 and IL-4 induce accessory functions of antigen-presenting cells. 210 7

Theileria parva-specific bovine BoT4+ Th cell clones were used to characterize Ag associated with T. parva schizont-infected lymphoblastoid cells. All of the clones tested responded to cells infected with the immunizing (Muguga) as well as heterologous stocks of T. parva, indicating that the T cells are specific for an Ag shared by several geographically diverse parasites. The response was apparently MHC-restricted, and induced by Ag expressed on the infected cell surface. In the presence of autologous APC, the clones were also stimulated by a soluble high speed supernatant (HSS), but not by a schizont membrane-enriched, subcellular fraction prepared from homogenates of infected cells. The clones produced IFN-gamma and T cell growth factor in response to HSS. The soluble Ag was absent in cells from which schizonts had been eliminated by treatment with the anti-theilerial drug, parvaquone. Fractionation of HSS by hydroxylapatite chromatography revealed two antigenic peaks that separated from the majority of the protein. Fractionation of HSS by gel filtration with the use of HPLC revealed several peaks of activity ranging in Mr from 270 kDa to less than 5 kDa. Further fractionation of HSS by both hydroxylapatite chromatography and gel filtration yielded three major peaks of activity (Mr 43, 12, 4.2 kDa). We conclude that a T cell-dependent schizont-associated soluble Ag is also expressed on the surface of T. parva-infected cells.
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PMID:Recognition of soluble Theileria parva antigen by bovine helper T cell clones: characterization and partial purification of the antigen. 213 83

We have analyzed the ability of human gamma+/delta+ T cells to recognize a nominal antigen in association with MHC molecules. A TT-specific T cell line with approximately 40% gamma+/delta+ T cells was established from a hyperimmunized donor, D.F., by stimulation with antigen and autologous APC. Three DF-derived gamma+/delta+ clones were CD8+ as determined by immunofluorescence staining, and by Southern and Northern blotting with probes detecting delta chain rearrangement and delta and gamma chain transcripts, respectively. The gamma+/delta+ clones responded to stimulation with TT, but not TNP-BSA, and autologous APC by proliferation and IFN-gamma production. No proliferation or IFN-gamma production was detected when TT-specific T cell clones were stimulated with either TT or autologous APC only. The response to TT was enhanced by addition of exogenous IL-2. The use of allogeneic APC from 19 donors sharing one HLA-determinant with the autologous donor D.F., showed that the gamma+/delta+ T cells responded to TT with HLA-DR4-related restriction as measured by proliferation and IFN-gamma production. These results demonstrate that gamma/delta receptors can recognize non-MHC-encoded foreign antigen in a self-MHC-restricted fashion.
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PMID:Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. 246 70


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