Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that the progressive deletion of CD4+ T cells in the course of infection due to human immunodeficiency virus (HIV) may be mediated in part by interaction with a superantigen inherent in an HIV protein. Consequently, selective loss of CD4+ cells with a T cell receptor V beta-chain capable of interaction with superantigen would produce a CD4+ population less or totally unresponsive to superantigen such as staphylococcal enterotoxins B and A (SEB and SEA respectively), but not to other mitogens such as concanavalin A, anti-CD3 (OKT3), or pokeweed mitogen. We tested this hypothesis by comparing the proliferative response of SEB and SEA with the other mitogens for 25 controls, 20 HIV+, and 15 donors with acquired immune deficiency syndrome (AIDS). We found that peripheral blood mononuclear cells, as well as the CD4+ and CD8+ subsets from both HIV+ and AIDS sources, the degree of suppression of mitogenesis for SEB and SEA was approximately equal to or less than that of the other mitogens. Moreover, suppression of HIV+ CD4+ and CD8+ T cell responses to SEB and SEA was equal (26%). If HIV superantigens exist, our data suggest that they are not responsible for the selective depletion of the CD4+ T cell subset as evaluated by SEB and SEA specificity.
 ...
PMID:Proliferative response of CD4+ and CD8+ T cell subsets from Hispanics with HIV+ and AIDS: the superantigen hypothesis. 790 21

To study the functional integrity of T cells from human immunodeficiency virus type 1 (HIV-1)-infected persons, CD4+ and CD8+ cells were examined for proliferation and secretion of interleukin-2 (IL-2) in response to staphylococcal superantigens and antibodies to CD3 and the alpha beta T cell receptor. A functional defect within CD8+ but not within CD4+ cells from HIV-1-infected persons was observed. Within CD8+ cells, proliferation and secretion of IL-2 was restricted to cells expressing the costimulatory molecule CD28. Such cells were proportionally reduced in HIV-1-infected persons. In patients with advanced immunodeficiency, however, evidence of functional derangement was found also within the CD28+ CD8+ cells. In a cross-sectional study of 73 HIV-infected persons and 15 controls, a significant correlation was observed between the number of CD28+ CD8+ cells and the presence of HIV-related disease. Our results suggest that regulation of expression of CD28 may play an important role in the immunopathogenesis of AIDS.
 ...
PMID:Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: functional and clinical correlations. 790 40

The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS. The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific V beta genes. To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 HIV+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V beta gene expression. In contrast to a recent study, the results presented here fail to provide evidence that selective loss of V beta-bearing T cells occurs in HIV+ individuals. Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing V beta subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen. Collectively, these data suggest that CD4 loss in HIV patients does not occur in a V beta-selective, superantigen-mediated fashion.
 ...
PMID:T cell receptor V beta repertoire in HIV-infection individuals: lack of evidence for selective V beta deletion. 809 57

Viral superantigens (SAg) were shown in mice to induce anergy and deletion of T cells bearing specific T cell receptor V beta subsets, these perturbations being mainly restricted to CD4+ T cells. In accordance with this model, a putative HIV-associated SAg could contribute to the pathogenesis of HIV-1 infection and AIDS. To reveal the presence of this putative molecule, three study protocols were designed that relied on the fact that similarity of the expressed V beta repertoire of a given pair of individuals is proportional to the relative likeness of their MHC background: (1) by using a quantitative PCR technique that allows simultaneous typing of 24 V beta families, the V beta repertoires of HIV-discordant monozygotic twins were compared; (2) the V beta repertoire found in lymph nodes of HIV-infected subjects was contrasted to that found in peripheral blood of the same individuals; (3) the V beta repertoire of a cohort of HIV-infected mothers was compared with that of their HIV-infected and uninfected children. Results from these approaches revealed that significant perturbations of the TCR V beta repertoire were taking place in HIV-infected subjects, and that these alterations were restricted to T cells expressing specific V beta s. These results are consistent with the presence of an HIV-associated SAg in HIV-1 infection.
 ...
PMID:The T cell receptor V beta repertoire in HIV-1 infection and disease. 810 62

Individuals infected with HIV have elevated numbers of total and activated CD8+ lymphocytes in peripheral blood. CD8+ lymphocytes from HIV-infected individuals have been shown to mediate non-human histocompatibility-linked antigen (HLA)-restricted suppression of viral replication, HLA-restricted killing of cells expressing HIV antigens, and killing of uninfected lymphocytes. We studied CD8+ T lymphocytes that lysed autologous CD4+ lymphocytes. heterologous CD4+ lymphocytes from HIV-infected individuals and uninfected CD4+ lymphocytes. Killing in all cases required T cell receptor (TCR)-mediated recognition or triggering. However, these CD8+ cytotoxic T lymphocytes (CTL) killed HLA class I mismatched CD4+ lymphocytes and CD4+ lymphocytes treated with a MoAb against HLA-A, B and C antigens (PA2.6) which blocks HLA class I-restricted killing. HLA class II-negative CD4+ T lymphoma cells (CEM.NKR) were also killed by anti-CD3 inhibited CTL. Stimulation of peripheral blood lymphocytes (PBL) from HIV-infected individuals, but not uninfected controls, with concanavalin A (Con A) and IL-2, induced non-HLA-restricted TCR alpha beta+, CD8+ CTL which lysed CD4+ lymphocytes. Activation of CD4+ lymphocytes increased their susceptibility to CD8+ CTL-mediated lysis. In HIV infection, a population of non-HLA-restricted CTL which lyse activated CD4+ lymphocytes is expanded. The expansion of CTL with unusual characteristics is interesting, because the stimulus for this expansion is unknown. CTL which recognize activated CD4+ cells could play a role in immune regulation and the pathogenesis of AIDS.
 ...
PMID:Lysis of CD4+ lymphocytes by non-HLA-restricted cytotoxic T lymphocytes from HIV-infected individuals. 810 17

Langerhans cells (LC) belong to the dendritic cell family and represent the principal antigen presenting cells populating squamous epithelia. We have reported the presence of human immunodeficiency virus Type 1 (HIV-1) proviral DNA and RNA in purified LC from the epidermis of seropositive patients. The aim of this study was to quantify HIV-1 proviral DNA in LC of infected patients using a competitive polymerase chain reaction (PCR) assay. Bulk epidermal cell (EC) suspensions were obtained from the skin of nine AIDS patients and six seronegative subjects. Purified LC and LC-depleted EC were prepared by immunomagnetic separation using an anti-CD1a monoclonal antibody. LC preparations did not contain T cells, as assessed by reverse transcription PCR analysis of the T cell receptor beta-chain gene (C region). In addition, no CD14+ cells could be detected in LC fractions by immunostaining of cytospin preparations. To quantify HIV-1 DNA, a new competitive PCR system was devised using SK145/150 as primers (gag) and a competitor plasmid DNA with a modified sequence (209 instead of 142 bp). The number of HIV-1 DNA copies found in the LC of AIDS patients ranged from 107 to 3,645/10(5) LC. In contrast, LC-depleted EC from the same subjects were all negative. The results indicate that in AIDS patients the frequency of infected LC is comparable to that reported for peripheral blood CD4+ T cells.
 ...
PMID:Quantitation by competitive PCR of HIV-1 proviral DNA in epidermal Langerhans cells of HIV-infected patients. 810 64

An increased ratio of T helper type 2 (Th2)- vs Th1-like cells contributes to the immune dysregulation in allergic disease situations and in many chronic infections, including AIDS. Th2-type immune responses are characterized by Th cells that produce increased levels of interleukin-4 (IL-4) and decreased levels of interferon gamma (IFN-gamma). The induction of either a Th1- or a Th2-like phenotype may be critically controlled by the antigen-presenting cells and their cytokines, e.g., IFN-alpha. In this study we have determined the frequencies of potential IL-4- and/or IFN-gamma-producing T cells in the peripheral blood of randomly selected healthy individuals, and analyzed whether IFN-alpha controls IL-4 and/or IFN-gamma production. Purified CD4+ or CD8+ T cells were stimulated for 24 h via the T cell receptor/CD3 complex in the presence or absence of IFN-alpha, and single IL-4- and IFN-gamma-secreting cells were detected in enzyme-linked immunospot assays. In the absence of IFN-alpha, CD4 cells produced IFN-gamma at frequencies of 1:50-300, and produced IL-4 at frequencies of 1:110-<1:100,000. Addition of IFN-alpha during the activation of CD4 cells increased the levels of IFN-gamma mRNA. As a consequence, the numbers of IFN-gamma-producing CD4 cells and the amounts of secreted IFN-gamma increased 10-fold. In contrast, IFN-alpha did not increase the frequency of IL-4-secreting CD4 cells. In the absence of IFN-alpha, addition of exogenous IL-4 to cultures of CD4 cells suppressed IFN-gamma secretion by 70%. However, in the presence of IFN-alpha, IL-4 did not display any suppressive effect. Compared with CD4 cells, CD8 cells produced IFN-gamma more frequently (1:5-10) but IL-4 less frequently (1:5,300 to < 1:100,000). IFN-alpha did not display any effect on the frequency of either IFN-gamma or IL-4 production by CD8 cells. Taken together the results indicate that IFN-alpha increases the frequency of IFN-gamma-secreting CD4 Th cells and antagonizes the suppressive effect of IL-4 on IFN-gamma production. As a consequence, IFN-alpha may favor the induction and maintenance of Th1-like cells and thereby counteract Th2-driven allergic immune responses.
 ...
PMID:Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells. 822 12

Recognition that the murine mammary tumor C-type retrovirus and the replication-defective murine leukemia virus have "superantigen" properties raises the specter that human immunodeficiency virus might also generate T cell impairment and destruction as a result of inherent superantigen properties. The observation that individuals with AIDS lack the expression of several T cell receptor V beta-chain genes lends support to this hypothesis. Staphylococcal exotoxins represent another class of superantigen with a similar ability to stimulate large numbers of T cells bearing specific T cell receptor V beta-chain types. To examine the hypothesis that T cells from HIV-infected individuals may be exposed to a superantigen during the infection process, we have compared the ability of T cells from asymptomatic HIV-infected donors and healthy donors to respond to stimulation with several known staphylococcal exotoxin superantigens. Following in vitro stimulation with staphylococcal enterotoxin D and staphylococcal enterotoxin E, asymptomatic HIV-infected individuals responded with a significantly different T cell receptor V beta-chain usage to that observed for healthy individuals. This skewed V beta-chain usage is likely to reflect preferential conditioning of T cells bearing specific V beta-chains as a result of HIV infection, supporting the hypothesis of superantigen involvement early in the course of infection.
AIDS Res Hum Retroviruses 1993 Mar
PMID:T cell response to staphylococcal superantigens by asymptomatic HIV-infected individuals exhibits selective changes in T cell receptor V beta-chain usage. 847 14

The concept that HIV causes AIDS only by directly killing CD4 cells has been questioned by a number of investigators. There has been experimental support for a number of indirect mechanisms such as apoptosis, anergy, superantigen-induced cell proliferation and depletion, defective signaling, molecular mimicry, and autoimmunity. In this article we review the available evidence in support of these theories and suggest that in spite of their apparent differences, signaling by HIV through the T cell receptor could initiate the markedly different responses of activation, anergy, and apoptosis. However, the unifying mechanism as to how this is achieved remains unclear. It is likely that more than one of these mechanisms are involved in CD4 cell depletion during different phases of the disease. Understanding these mechanisms and their role in HIV pathogenesis would be important in new vaccine and therapeutic approaches.
AIDS Res Hum Retroviruses 1993 Mar
PMID:New concepts in AIDS pathogenesis. 847 20

Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play a central role in inducing immunoregulatory disorders after HIV infection. The apoptotic death of normal human peripheral blood mononuclear cells was induced by priming with gp120 followed by stimulation with an anti-T cell receptor (TCR) antibody. Tumor necrosis factor-alpha produced by gp120-binding macrophages may be important to induce this cell death. Treatment of gp120-primed cells with an immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death, and this blocking effect of FK506 was concentration dependent. FK506 did not have any influence on cell growth and viability over the range of concentrations tested. These findings suggest that FK506 is a potentially useful drug in delaying the onset of AIDS after HIV infection.
 ...
PMID:Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced by HIV-1 gp120. 857 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>