Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Though the functional roles of human CD2 are well characterized, murine studies have been lacking until very recent years. Our previous work showed that a mAb against the T11(1)-like domain of CD2 clearly inhibited T cell proliferation induced by mitogenic and allo-antigenic stimuli, but the degree of inhibition was much smaller than had been demonstrated in the human system. In the present study, we observed functional aspects of murine CD2 on CD4+ T cell clones. It was shown that all T cell clones tested were CD2-positive, and that proliferation induced by APC + Ag was inhibited by anti-CD2 mAb. The maximum inhibition was also partial (40-60% inhibition) but CD2-mediated inhibition was observed even at concentrations as low as 0.2 microgram/ml. In contrast to the APC + Ag stimulation, the proliferation induced by lymphokines or immobilized anti-CD3 mAb was not inhibited at all. Taken together, these findings indicate that: (1) CD2 is also involved in the interaction between HTL and APC in murine system; but (2) perturbation of murine CD2 does not influence TCD/CD3- and lymphokine-mediated signal transduction.
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PMID:Characterization of inhibitory effects of an anti-murine CD2 monoclonal antibody on the proliferation of T cell clones. 167 15

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

Four regulatory phenomena appear to regulate differentially the activation of TH1, TH2, and CTL clones. First, IFN-gamma selectively inhibits proliferation of TH2 but not TH1 cells; lymphokine production by TH2 cells is not affected by IFN-gamma. In addition, when fresh OVA-specific HTL clones are derived in the presence of rIL-2 TH2 cells are preferentially obtained, whereas TH1 cells predominate if cloning is performed in rIL-2 plus rIFN-gamma. These results suggest that the presence of IFN-gamma during the course of an immune response would result in the preferential expansion of HTL of the TH1 phenotype. Proliferation of CTL clones is not influenced by IFN-gamma. Second, different APC populations appear to differentially activate TH1 and TH2 clones. Purified splenic B cells stimulate optimal proliferation of TH2 but not TH1 cells, whereas macrophage/dendritic cells appear to stimulate optimal proliferation of TH1 but not TH2 cells. Since both APC types stimulate lymphokine production by each of the HTL subsets, these results suggest the existence of TH1- and TH2-specific cofactors for growth. Third, high doses of immobilized anti-CD3 mAb inhibit IL-2-dependent proliferation of TH1 but not TH2 clones. Since this effect appears to require calcium, this observation suggests that TCR-mediated signalling events might differ between the two HTL subsets. Indeed, little or no increase in [Ca++]i can be detected in TH2 clones stimulated with Con-A, while such an increase is easily discernible in TH1 cells. Although high concentrations of immobilized anti-CD3 mAb inhibit IL-2-dependent proliferation of CTL clones, proliferation of these cells in response to immobilized anti-CD3 alone reaches a plateau. Since activation with anti-CD3 is thought to mimic antigenic stimulation, these results suggest that antigen concentration may play a role in determining which predominant T-cell types proliferate in a particular immunological situation. Fourth, pretreatment of TH1 cells, but not TH2 cells or CTL, with IL-2 results in decreased lymphokine production and proliferation in response to subsequent stimulation via the TCR. This antigen-responsive state appears to involve a defect in calcium-dependent signalling, providing additional evidence for different signalling mechanisms in TH1 and TH2 clones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of T-cell activation: differences among T-cell subsets. 253 16