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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

We have previously shown that HIV-1 seropositivity is associated with an increase in the difference between the number of CD3+ lymphocytes and the total number of CD4+ and CD8+ lymphocytes [CD3 - (CD4 + CD8)] among peripheral blood lymphocytes (PBL). To investigate the cellular basis of this increase, PBL from seronegative (SN) and AIDS-free seropositive (SP) homosexual men and intravenous drug users were analyzed by two-color flow cytometry. Results showed that SP compared to SN manifested the expected elevation in calculated [CD3 - (CD4 + CD8)] cells (87 vs 28 cells/mm3; P less than 0.001). Only small differences in lymphocyte populations that could contribute to this increase were observed, namely lymphocytes expressing the CD3+CD4-CD8-phenotype (67 vs 56 cells/mm3; P greater than 0.10) or the CD8dim phenotype (135 vs 142 cells/mm3; P greater than 0.10). However, SP had significantly lower numbers of cells expressing the CD56+CD3- phenotype characteristic of natural killer cells (81 vs 170 cells/mm3; P less than 0.001) and significantly higher numbers of T cells expressing the gamma delta T cell receptor (TCR) (81 vs 62 cells/mm3; P = 0.10). The latter difference was primarily due to higher numbers of cells coexpressing gamma delta-TCR and low levels of CD8 (27 vs 15 cells/mm3; P = 0.009). These data suggest that HIV-1 seropositivity is associated with low numbers of natural killer cells and high numbers of CD8+ gamma delta-TCR lymphocytes. Changes in these populations may reflect altered host defense against HIV-1 or altered T cell kinetics in the presence of HIV-1 infection.
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PMID:Flow cytometric analysis of gamma delta T cells and natural killer cells in HIV-1 infection. 182 68

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.
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PMID:A subset of gamma delta lymphocytes is increased during HIV-1 infection. 182 86

To investigate the effects of persistant human immunodeficiency virus (HIV) infection on T cell reactivity, functional properties of peripheral blood T cells from HIV-seropositive homosexual men in various stages of infection were studied. T cell activation via CD3 resulting in proliferation and differentiation was measured in a model system independent of accessory cells, using immobilized anti-CD3 monoclonal antibodies (mAb). T cells from HIV-infected asymptomatic men had a decreased proliferative response compared to HIV-negative controls. T cells from AIDS-related complex (ARC) and AIDS patients, compared to T cells from asymptomatic HIV-infected men, had a significantly lower proliferative response to anti-CD3 mAb. This diminished response to anti-CD3 mAb was shown to be due to decreased interleukin (IL) 2 production and could be enhanced by co-stimulation with anti-CD28 mAb or by adding IL 2. Anti-CD3-induced generation of cytotoxic T lymphocytes was fully intact in early infection but was severely decreased in T cells from ARC and AIDS patients. Cytotoxic activity could be restored to near normal levels after co-stimulation with either anti-CD28 mAb or IL 2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL 2 production after stimulation via the CD3/T cell receptor complex. In early HIV infection this seems to be predominantly caused by a specific loss of memory T cells. However, in later stages of infection when both naive and memory T cell subsets are depleted, resulting in a normal naive/memory T cell ratio, T cell functions further deteriorate probably due to intrinsic activation defects. These findings may be of pathogenic relevance since diminished T cell reactivity may facilitate spreading and replication of virulent HIV variants heralding development of ARC and AIDS.
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PMID:Selective loss of T cell functions in different stages of HIV infection. Early loss of anti-CD3-induced T cell proliferation followed by decreased anti-CD3-induced cytotoxic T lymphocyte generation in AIDS-related complex and AIDS. 216 75

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE.
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PMID:An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. 221 48

To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the alpha/beta T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2. 238 2

A hypothesis is presented in which HIV infection leads to immunodeficiency through indirect subversion of critical T cell regulatory mechanisms. Acting at the T cell receptor complex (TCR), viral components (gp120) mimic the natural ligands of CD4, molecules of the major histocompatibility complex (MHC), and deliver physiologically active, inappropriate signals resulting in generalized, uncontrolled lymphocyte activation, or "panergy." Clinical manifestations of panergy include autoimmune phenomena, lymphadenopathy, hyperglobulinemia, and symptoms mediated by lymphokines. Immunologic unresponsiveness occurs early in HIV infection prior to T cell depletion because activated cells do not respond to further stimulation. Ultimately, activation disrupts T cell homeostasis by interference with the generation of memory cells ("imnesia") and leads to net T cell loss, clonal deletion, and the development of AIDS. The clinical and immunologic features of HIV disease and AIDS are reviewed from this perspective. This hypothesis is consistent with the paucity of infected T cells, the clinical findings of both AIDS-related complex (ARC) and frank AIDS, the prolonged "incubation period," and a role for antigen-specific cofactors. Based on this view of HIV pathophysiology, therapeutic modalities should avoid immune stimulation and seek to block aberrant gp120 signals at CD4 and eliminate HIV-infected cells.
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PMID:AIDS as immune system activation. II. The panergic imnesia hypothesis. 240

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS.
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PMID:Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion. 247 Jul 86


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