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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitory effects of human immunodeficiency virus (HIV) on T lymphocyte function have been linked to perturbation of signaling through the T cell antigen receptor-CD3 complex. Comparative biochemical analyses of signaling responses were performed in T cells that were either uninfected or chronically infected with the HIV-1/IIIB strain. Stimulation with antibodies to CD3 triggered both Ca2+ accumulation and phosphoinositide hydrolysis responses that were equivalent in uninfected and infected cells. Treatment with anti-CD3 or with phorbol diester also stimulated serine phosphorylation of CD4 molecules in uninfected T cells. However, phosphorylation of CD4 was not observed after anti-CD3 treatment in HIV-infected T cells despite normal phosphorylation responses to phorbol diester. Identical results were obtained using a T cell line that was infected with an env (gp160/120-) HIV-1 defective variant. These studies indicate that infection with HIV-1 inhibits the activation of protein kinase associated with the T cell receptor-CD3 complex by a mechanism which is independent of viral env protein components.
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PMID:Inhibition of T cell antigen receptor-dependent phosphorylation of CD4 in human immunodeficiency virus type 1 infected cells. 131 Sep 88

In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.
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PMID:Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. 134 69

The repertoire of V regions of alpha/beta+ T cell receptor (TcR) on CD4+ and CD8+ T cells from the peripheral blood of six patients with a novel X-linked combined immunodeficiency was investigated by flow cytometry. The relative frequencies of V region subfamilies V alpha 2a on CD4+ T lymphocytes and V beta 5b and V beta 12a on CD8+ T lymphocytes from the peripheral blood from the affected males were decreased significantly. Also, the relative frequencies of certain other V region subfamilies on CD4+ or CD8+ T cells from the peripheral blood of some patients were either considerably below or above the ranges found in normal subjects. Although there may be other explanations including an extrathymic event, we suggest that the abnormalities in the TcR repertoire of peripheral blood T cells are consistent with a dysregulation of the intrathymic maturation/selection of T cells that leads to deficiencies in T cell populations in the peripheral blood of males with this disease.
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PMID:Repertoire of V alpha and V beta regions of T cell antigen receptors on CD4+ and CD8+ peripheral blood T cells in a novel X-linked combined immunodeficiency disease. 134 30

Superantigens (SAg) interact with T lymphocytes bearing particular V beta sequences as part of their T cell receptor (TcR). The interaction, however, requires the presence of major histocompatibility complex (MHC) class II molecules on antigen-presenting cell (APC). In peculiar circumstances, MHC class II+ T cell clones (TCC) have been shown to present peptides and selected antigens interacting with antigen-specific TCC in the absence of APC. In this report we studied the capacity of SAg to mediate a T-T cell interaction, investigating the TCC ability to present a panel of staphylococcal enteroxins (SE) independently of the presence of added APC. Upon exposure to a broad range of SE concentrations, MHC class II+ TCC showed an intense proliferative response even in the absence of professional APC. Diverse SE optimally stimulated responder TCC at different concentrations. The proliferation was inhibited by anti-DR monoclonal antibodies, both in the presence and in the absence of APC. The SE activation of TCC in the absence of APC induced the same series of phenotypic variations as that observed following the TCC stimulation with APC. Irradiated TCC efficiently presented membrane-bound SE to responder TCC as well as professional APC. These results show that a single cell of a given clone effectively presents the SE to other cells of the same clone, and provide evidence that SAg can efficiently mediate T-T cell interaction. In addition, the possibility also exists that one cell of the clone can actually undergo an auto-stimulation via SAg-mediated interactions between its own TcR and MHC class II molecule. It has recently been suggested that the V beta-selective depletion of T cells observed in acquired immunodeficiency syndrome (AIDS) patients might be a consequence of the interaction between a human immunodeficiency virus (HIV)-encoded SAg and T cells expressing a SAg complementary V beta. We suggest that the hypothesized HIV-encoded SAg might mediate T-T cell interactions that could play a relevant role in the V beta-selective depletion of T lymphocytes observed in HIV-infected patients.
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PMID:Presentation of superantigen by human T cell clones: a model of T-T cell interaction. 135 48

During human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4+ population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4+ cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.
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PMID:Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. 140 55

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells.
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PMID:T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. 151 49

Increased proportions of the small lymphoid subset expressing T cell receptor (TCR) gamma delta occur in different infectious diseases, particularly in mycobacterial infections. In this study the two main subsets of TCR gamma delta+ cells in peripheral blood mononuclear cells (PBMC) of 54 patients with human immunodeficiency virus type 1 infection were analyzed. These subsets were defined by indirect immunofluorescence techniques and FACS analysis using BB3 and A13 monoclonal antibodies, which specifically react with V delta 2- and V delta 1-encoded forms of TCR gamma delta. The proportion of BB3+(V delta 2+) and A13+(V delta 1+) cells was analyzed in purified PBMC populations. Patients were stratified according to Walter Reed (WR) clinical stage. A sharp increase in percentage of A13+(V delta 1+) cells was observed in all stages of the disease. In addition, a strict correlation was found with stage of the disease and percentage of CD8+ PBMC. An inverse correlation was found with the proportion of CD4+ PBMC. An early (WR2) inversion of the V delta 2-to-V delta 1 ratio was consistently detected even before the inversion of the CD4-to-CD8 ratio.
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PMID:Selective increase of a subset of T cell receptor gamma delta T lymphocytes in the peripheral blood of patients with human immunodeficiency virus type 1 infection. 153 37

Members of the Ets family of proto-oncogenes encode sequence-specific transcription factors that bind to a purine-rich motif centered around a conserved GGA trinucleotide. Ets binding sites have been identified in the transcriptional regulatory regions of multiple T cell genes including the T cell receptor alpha and beta (TCR-alpha and -beta) enhancers and the IL-2 enhancer, as well as in the enhancers of several T cell-trophic viruses including Maloney sarcoma virus, human leukemia virus type 1, and human immunodeficiency virus-2. T cells express multiple members of the Ets gene family including Ets-1, Ets-2, GABP alpha, Elf-1, and Fli-1. The different patterns of expression and protein-protein interactions of these different Ets family members undoubtedly contribute to their ability to specifically regulate distinct sets of T cell genes. However, previous studies have suggested that different Ets family members might also display distinct DNA binding specificities. In this report, we have examined the DNA binding characteristics of two Ets family members, Ets-1 and Elf-1, that are highly expressed in T cells. The results demonstrate that the minimal DNA binding domain of these proteins consists of adjacent basic and putative alpha-helical regions that are conserved in all of the known Ets family members. Both regions are required for DNA binding activity. In vitro binding studies demonstrated that Ets-1 and Elf-1 display distinct DNA binding specificities, and, thereby interact preferentially with different naturally occurring Ets binding sites. A comparison of known Ets binding sites identified three nucleotides at the 3' end of these sequences that control the differential binding of the Ets-1 and Elf-1 proteins. These results are consistent with a model in which different Ets family members regulate the expression of different T cell genes by binding preferentially to purine-rich sequences that share a GGA core motif, but contain distinct flanking sequences.
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PMID:Evolutionarily conserved Ets family members display distinct DNA binding specificities. 156 4

Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is though to affect normal cell signaling, tyrosine phosphorylation may be associated with HIV cytopathicity. In both HIV-infected cells and transfected cells that stably express HIV envelope glycoproteins undergoing HIVgp41-induced cell fusion, a 30-kilodalton protein was phosphorylated on tyrosine with kinetics similar to those of syncytium formation and cell death. When tyrosine phosphorylation was inhibited by the protein tyrosine kinase inhibitor herbimycin A, envelope-mediated syncytium formation was coordinately reduced. These studies show that specific intracellular signals, which apparently participate in cytopathicity, are generated by HIV and suggest strategies by which the fusion process might be interrupted.
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PMID:Participation of tyrosine phosphorylation in the cytopathic effect of human immunodeficiency virus-1. 157 May 14

We report the consequences of low expression of the T cell receptor (TcR)/CD3 complex by T lymphocytes from a 4-year-old boy with a mild immunodeficiency. TcR/CD3 expression was found to be deficient on both resting and activated T cells, using both anti-CD3 and anti-TcR alpha/beta monoclonal antibodies. As shown by immunofluorescence and immunoprecipitation studies, residual expression (corresponding to about 10% of normal) was detectable on resting and activated TcR alpha/beta+ T cells. Other T cell membrane receptors were normally expressed. The functional consequences of this TcR/CD3 expression deficiency included an absence of T cell proliferation, interleukin 2 receptor expression and calcium flux following anti-CD3 and anti-CD2 antibody-triggered T cell activation. Antigen (tetanus toxoid, Candida and allogeneic cell)-induced proliferation was detectable. In contrast, cytotoxic T cell activity towards allogeneic cells was deficient. These findings shed light on the function of the TcR/CD3 complex and indicate that the expression of a limited number of TcR/CD3 receptors may be sufficient to trigger antigen-specific T cell activation (and, possibly, differentiation) and that anti-CD3 antibody-induced T cell activation differs somewhat from antigen/major histocompatibility complex molecule-induced activation. These results also confirm that the CD2 pathway of T cell activation is CD3 dependent.
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PMID:Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation. 167 69


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