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)

We have previously reported the cloning of a novel cytokine, IFN-gamma-inducing factor (IGIF), which shared some biologic activities with IL-12. In this study, we analyzed the effects of murine IGIF on the activation of T cells, and compared the effects with those of IL-12. IGIF alone had no effect on the activation of T cell lines or Th1 clones, while IGIF increased the IFN-gamma production by antigen-stimulated T cell lines, but had no effect on IL-4 or IL-10 production. As reported with IL-12, IGIF served as a costimulatory factor for Th1 clones stimulated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to augment IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation of the Th1 clones, whereas IGIF had little or no effect on the IL-4 production and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF synergized with IL-12 to further augment the IFN-gamma production of the Th1 clones. Even in the presence of saturated amounts of IL-12, IGIF still augmented the IFN-gamma production and proliferation and enhanced the IL-2R alpha-chain expression of the Th1 clones. In contrast with IL-12, IGIF induced IL-2 production by Ag- or anti-CD3-stimulated Th1 clones. These two findings indicate that IGIF and IL-12 are utilizing different signal transduction pathways. We also found that IGIF as well as IL-12 was endogenously released through interaction between Th1 cells and spleen cell APC in the presence of specific Ag, and that it regulated IFN-gamma production. These results further suggest that IGIF may act as an immunoregulatory factor in the immune response.
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PMID:IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. 902 88

Immune privilege in the eye is a dynamic state in which the immune response to ocular Ags is molded and modified by the eye itself. Immune privilege correlates with systemic alterations in the immune response such that deviant forms of immunity emerge. The eye itself contributes to immune deviation, in part by displaying unique immunoregulatory factors in aqueous humor and expressed on ocular cells. When T cells encounter Ag in the eye, they can become anergic, undergo apoptosis, secrete TGF-beta, and/or release soluble regulatory factors containing the TCR alpha-chain. Ags taken up by indigenous APC escape the eye and reach the spleen where they activate a unique spectrum of Ag-specific T and B cells. The absence of systemic delayed hypersensitivity and complement-fixing Abs in this deviant response probably relates to the fact that inflammation is deleterious to vision and leads to blindness. Immune privilege is the eye's way of protecting its vital function from the ravages of immunopathogenic injury.
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PMID:Immune deviation in relation to ocular immune privilege. 910 14

The mRNA and protein expression of the alpha- and beta-chains of IFN-gammaR were evaluated on a panel of human Th1 and Th2 clones. When cultured in IL-2-conditioned medium, both types of clones expressed mRNA for the alpha- and beta-chains, and both chains were present in the cytoplasm. Membrane expression of the alpha-chain was higher on Th2 than on Th1, whereas the beta-chain was poorly expressed on both types but increased following IL-2 withdrawal or PHA stimulation. In addition, both types of clones overexpressed MHC class I glycoproteins following IFN-gammaR triggering by exogenous IFN-gamma, although the kinetics was slower in Th1, and this exposure induced mRNA for IRF-1. When their TCR was triggered in the absence of APC, Th1 only underwent apoptosis. This activation-induced apoptosis was prevented by blocking of the alpha-chain or by IFN-gamma neutralization. Addition of IFN-gamma triggered the apoptosis of Th2 clones. Apoptosis of both types of clones was mediated by autocrine or exogenous IFN-gamma through the up-regulation of Fas-L expression, since anti-IFN-gammaR alpha mAb inhibited its expression on Th1 and exogenous IFN-gamma increased its expression on Th2. These results indicate that activated human Th1 and Th2 lymphocytes express IFN-gammaR alpha- and beta-chains and are both sensitive to signals provided by IFN-gamma. Data also suggest that IFN-gamma is critical for switching off their responses.
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PMID:Expression and role in apoptosis of the alpha- and beta-chains of the IFN-gamma receptor on human Th1 and Th2 clones. 920 Apr 56

Requirements for the activation and proliferation of gammadelta T cells were investigated. Maximum numbers of gammadelta T cells expressed the IL-2R alpha-chain after 6-h Con A stimulation in peripheral blood, efferent lymph, and afferent lymph. In comparison, IL-2R alpha-chain expression on CD4 T cells only reached maximum levels in response to Con A stimulation in peripheral blood and afferent lymph populations. Analysis of enriched gammadelta T cells demonstrated that Con A-induced expression of the IL-2R alpha-chain was independent of APC. Together, these data suggest that the requirements for gammadelta T cell activation are less stringent than those for alphabeta T cell activation. Unfractionated peripheral blood, efferent lymph, and afferent lymph cell populations proliferated in response to Con A alone. In contrast, enriched gammadelta T cells (CD4/CD8 depleted) from efferent lymph did not proliferate in response to Con A alone, but required the addition of IL-2. This requirement for exogenous IL-2 could be overcome by the addition of dendritic cells purified from afferent lymph. These results suggested that gammadelta T cells required costimulatory signals provided by APC to ensure the production of sufficient IL-2 to drive proliferation. CD28 and CTLA-4 mRNA were detected in efferent lymph and afferent lymph populations containing CD4 and CD8 T cells stimulated with Con A and IL-2 or with Con A alone, respectively. In contrast, negligible levels of these mRNA species were detected in efferent and afferent lymph populations devoid of CD4 and CD8 T cells. These results suggest that ovine gammadelta T cells may use alternative costimulatory pathways.
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PMID:Cellular requirements for the activation and proliferation of ruminant gammadelta T cells. 937 24

Experimental autoimmune myasthenia gravis (EAMG) can be induced in C57BL/6 (B6) mice by immunization with Torpedo californica acetylcholine receptor (tAChR). We had previously shown that pretreatment with a monomethoxypolyethylene glycol (mPEG) conjugate of myasthenogenic tAChR alpha-chain peptide alpha125-148 (mPEG-peptide) suppressed EAMG. In order to understand the mechanism involving T cells in the induction of this suppression, we have studied, in the present work, the in vitro responses of T cells from mPEG-peptide treated B6 mice after an initial tAChR injection to determine the early effect of mPEG-peptide treatment on these responses. Treatment with mPEG-peptide reduced the T cell responses to tAChR and several tAChR alpha-chain peptides. To further investigate the T cell helper function in vivo, we transferred T cells from B6 mice that received either mPEG-peptide or control PBS followed by two tAChR injections to non-immune B6 mice. T cell transfer from mPEG-peptide pretreated mice down regulated, in recipient mice, Ab induction (after cell transfer) and Ab production (after two tAChR injections) toward alpha-chain peptides. Treatment of B6 mice with mPEG-peptide did not alter the ability of their APC to present peptide alpha146-162 to peptide-specific B6 T cells. The results indicate that suppression of EAMG by treatment with mPEG-peptide is due to T cell involvement and not to a defect in APC function.
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PMID:T cells of mice treated with mPEG-myasthenogenic peptide conjugate are involved in protection against EAMG by stimulating lower pathogenic antibody responses. 1095 75

We investigated the effect of C4BP on APC-mediated inactivation of factor Va (FVa) in the absence and presence of protein S. FVa inactivation was biphasic (k(506) = 4.4 x 10(8) M(-)(1) s(-)(1), k(306) = 2.7 x 10(7) M(-)(1) s(-)(1)), and protein S accelerated Arg(306) cleavage approximately 10-fold. Preincubation of protein S with C4BP resulted in a total abrogation of protein S cofactor activity. C4BP also protected FVa from inactivation by APC in the absence of protein S. Control experiments with CLB-PS13, a monoclonal anti-protein S antibody, indicated that inhibition of FVa inactivation by C4BP was not mediated through contaminating traces of protein S in our reaction systems. Protection of FVa was prevented by a monoclonal antibody directed against the C4BP alpha-chain. Recombinant rC4BPalpha comprised of only alpha-chains also protected FVa, but in the presence of protein S, the level of protection was decreased, since rC4BPalpha lacks the beta-chain responsible for C4BP binding to protein S. A truncated C4BP beta-chain (SCR-1+2) inhibited protein S cofactor activity, but had no effect on FVa inactivation by APC in the absence of protein S. In conclusion, C4BP protects FVa from APC-catalyzed cleavage in a protein S-independent way through direct interactions of the alpha-chaims of C4BP with FVa and/or APC.
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PMID:C4b-binding protein protects coagulation factor Va from inactivation by activated protein C. 1108 9

The two main constraints that currently limit a broader usage of T cell therapy against viruses are the delay required to obtain specific T cells and the safety of the selection procedure. In the present work we developed a generally applicable strategy that eliminates the need for APC for timing reasons, and the need for infectious viral strains for safety concerns. As a model, we used the selection of T lymphocytes specific for the immunodominant CMV phosphoprotein pp65. PBMC from healthy seropositive donors were first depleted of IL-2R alpha-chain CD25(+) cells and were then stimulated for 24-96 h with previously defined peptide Ags or with autologous PBMC infected with a canarypox viral vector encoding the total pp65 protein (ALVAC-pp65). Subsequent immunomagnetic purification of newly CD25-expressing cells allowed efficient recovery of T lymphocytes specific for the initial stimuli, i.e., for the already known immunodominant epitope corresponding to the peptides used as a model or for newly defined epitopes corresponding to peptides encoded by the transfected pp65 protein. Importantly, we demonstrated that direct PBMC stimulation allowed recovery not only of CD8(+) memory T lymphocytes, but also of the CD4(+) memory T cells, which are known to be crucial to ensure persistence of adoptively transferred immune memory. Finally, our analysis of pp65-specific T cells led to the identification of several new helper and cytotoxic epitopes. This work thus demonstrates the feasibility of isolating memory T lymphocytes specific for a clinically relevant protein without the need to prepare APC, to use infectious viral strains, or to identify immunodominant epitopes.
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PMID:Purification of Ag-specific T lymphocytes after direct peripheral blood mononuclear cell stimulation followed by CD25 selection. I. Application to CD4(+) or CD8(+) cytomegalovirus phosphoprotein pp65 epitope determination. 1159 40

Superantigens are known to activate a large number of T cells. The SAg is presented by MHC class II on the APC and its classical feature is that it recognizes the variable region of the beta-chain of the TCR. In this article, we report, by direct binding studies, that staphylococcal enterotoxin (SE) H (SEH), a bacterial SAg secreted by Staphylococcus aureus, instead recognizes the variable alpha-chain (TRAV27) of TCR. Furthermore, we show that different SAgs (e.g., SEH and SEA) can simultaneously bind to one TCR by binding the alpha-chain and the beta-chain, respectively. Theoretical three-dimensional models of the penta complexes are presented. Hence, these findings open up a new dimension of the biology of the staphylococcal enterotoxins.
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PMID:Cutting edge: Evidence of direct TCR alpha-chain interaction with superantigen. 1770 82

In malignancies where no universally expressed dominant Ag exists, the use of tumor cell-based vaccines has been proposed. We have modified a mouse neuroblastoma cell line to express either CD80 (B7.1), CD137L (4-1BBL), or both receptors on the tumor cell surface. Vaccines expressing both induce a strong T cell response that is unique in that among responding CD8 T cells, a T effector memory cell (T(EM)) response arises in which a large number of the T(EM) express the alpha-chain of VLA-2, CD49b. We demonstrate using both in vitro and in vivo assays that the CD49b(+) CD8 T cell population is a far more potent antitumor effector cell population than nonfractionated CD8 or CD49b(-) CD8 T cells and that CD49b on vaccine-induced CD8 T cells mediates invasion of a collagen matrix. In in vivo rechallenge studies, CD49b(+) T cells no longer expanded, indicating that CD49b T(EM) expansion is restricted to the initial response to vaccine. To demonstrate a mechanistic link between the expression of costimulatory molecules on the vaccine and CD49b on responding T cells, we stimulated naive T cells in vitro with artificial APC expressing different combinations of anti-CD3, anti-CD28, and CD137L. Although some mRNA encoding CD49b was induced by combining anti-CD3 with anti-CD28 or CD137L, the highest level was induced when all three signals were present. This indicates that CD49b expression results from additive costimulation and that the level of CD49b message serves as an indicator of the effectiveness of T cell activation by a cell-based vaccine.
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PMID:Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L. 1880 64

Numerous studies have demonstrated that targeting immunogens to Fcgamma receptors (FcgammaR) on antigen (Ag)-presenting cells (APC) can enhance humoral and cellular immunity in vitro and in vivo. FcgammaR are classified based on their molecular weight, IgG-Fc binding affinities, IgG subclass binding specificity, and cellular distribution and they consist of activating and inhibitory receptors. However, despite the potential advantages of targeting Ag to FcR at mucosal sites, very little is known regarding the role of FcR in mucosal immunity or the efficacy of FcR-targeted mucosal vaccines. In addition, recent work has suggested that FcRn is present in the lungs of adult mice and humans and can transport FcRn-targeted Ag to FcgammaR-bearing APC within mucosal lymphoid tissue. In this review we will discuss the need for new vaccine strategies, the potential for FcR-targeted vaccines to fill this need, the impact of activating versus inhibitory FcgammaR on FcR-targeted vaccination, the significance of focusing on mucosal immunity, as well as caveats that could impact the use of FcR targeting as a mucosal vaccine strategy.
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PMID:Fc receptor-targeted mucosal vaccination as a novel strategy for the generation of enhanced immunity against mucosal and non-mucosal pathogens. 1968 86


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