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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined the impact of the predominantly Th2-type lymphokines interleukin 13 (IL-13) and interleukin 4 (IL-4) on acute infection of human bronchoalveolar macrophages with a macrophage-tropic isolate of human immunodeficiency virus type 1 (HIV-1). Addition of 0.01-10 ng of IL-4 or IL-13 per milliliters significantly blocked HIV-1 replication in infected cells, judging from levels of reverse transcriptase and p24 antigen in the supernatants of infected cells. Both IL-4 and IL-13 were almost as efficient as interferon-gamma (IFN-gamma) in preventing HIV-1 replication, when given in equivalent amounts. Moreover, neither IL-13 nor IL-4 interfered with the IFN-gamma-mediated enhancement of anti-HIV-1 activity in alveolar macrophages. Both IL-4 and IL-13 interfered with enhanced replication of HIV-1 in macrophages pulsed with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin 13 also prevented HIV-1 release from peripheral blood mononuclear cells in a cocultivation experiment with feeder cells from a seronegative subject. These data suggest that Th2-derived lymphokines have significant anti-HIV-1 activity in cells of the macrophage lineage, although they may enhance the susceptibility of HIV-1-infected subjects to some opportunistic pathogens.
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PMID:Interleukin 13 and interleukin 4 protect bronchoalveolar macrophages from productive infection with human immunodeficiency virus type 1. 798 85

Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients. The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells.
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PMID:T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection. 798 1

In vitro T-cell receptor-induced programmed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting T cells from HIV+ donors was substantially influenced by cytokines. Addition of exogenous recombinant "type 1" lymphokines interferon gamma and interleukin 2 (IL-2), as well as the macrophage-produced IL-12, which favor cell-mediated T-cell responses, blocks both systems of T-lymphocyte programmed cell death. In contrast, the "type 2" lymphokines IL-4 and IL-10, which favor antibody responses, either had no effect or enhanced these systems of in vitro T-cell programmed cell death. A role for endogenously produced cytokines was suggested by the inhibition of T-cell receptor-mediated death by antibodies against IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures containing monocytes. These results demonstrate that the functional properties of type 1 and type 2 cytokine classes may be further extended to include their effects on T-cell programmed cell death and their possible role in the pathogenesis of HIV infection.
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PMID:Type 1/type 2 cytokine modulation of T-cell programmed cell death as a model for human immunodeficiency virus pathogenesis. 799 40

In addition to the loss of CD4+ T cells in later stages of human immunodeficiency virus (HIV) infection, functional defects of Th cells can already be observed in early infection. Decreased interleukin (IL)-2 and interferon (IFN)-gamma production by CD4+ T cells and diminished delayed type hypersensitivity reactions are indicative for impaired Th1 responses. We studied the cytokine secretion patterns of T-cell clones (TCC) generated by mitogenic stimulation of CD4+ memory T cells. Compared with TCC from HIV-negative controls, TCC isolated from HIV-infected individuals consistently showed increased IL-4 production, often paralleled by increased IL-5 and decreased IFN-gamma production. This resulted in a decreased percentage of Th1 clones with an increase in Th0 clones. To rule out the influence of interindividual differences, we studied two individuals from whom cells were available before and after infection with HIV. Indeed, an increase in Th2 cytokine secretion was observed after HIV-infection. Loss of Th1 and enhanced Th2 responses might further curtail cellular responses resulting in deficiency of cellular immunity in HIV infection.
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PMID:Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection. 799 41

T cell functional defects are a common aspect of human immunodeficiency virus (HIV) infection. Moreover, it has been suggested that indirect mechanisms are involved in CD4+ cell depletion. Unresponsiveness to proliferative stimuli of lymphocytes incubated with HIV particles or with viral proteins is well documented. Nevertheless, drawing a clear picture of the anergy phenomenon is difficult because of several unresolved and controversial questions. Here we report that recombinant gp120 induces anergy in T helper lymphocytes cultured with different stimuli. The proliferative responses to interleukin (IL)-2, IL-4, IL-6, anti-CD2, anti-CD3 and phorbol 12-myristate 13-acetate are inhibited. Moreover, anergic cells show a different distribution in cell cycle phases as compared to control cells, leading us to suggest that the progression in the cell cycle is hampered and that a pre-mitotic block takes place. Furthermore, since chimpanzees are susceptible to HIV-1 infection without showing immunodeficiency signs, we analyzed the proliferation of chimpanzee lymphocytes without observing anergy in cells preincubated with gp120. Taken together, these results support the hypothesis that anergy plays an important role in HIV infection in vivo.
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PMID:Different proliferative response of human and chimpanzee lymphocytes after contact with human immunodeficiency virus type 1 gp120. 802 May 68

A switch from a T helper 1 (TH1) cytokine phenotype to a TH2 phenotype has been proposed as a critical element in the progression of human immunodeficiency virus (HIV) disease. Here, constitutive cytokine expression was analyzed in unfractionated and sorted cell populations isolated from peripheral blood and lymph nodes of HIV-infected individuals at different stages of disease. Expression of interleukin-2 (IL-2) and IL-4 was barely detectable (or undetectable) regardless of the stage of disease. CD8+ cells expressed large amounts of interferon gamma and IL-10, and the levels of these cytokines remained stably high throughout the course of infection. Furthermore, similar patterns of cytokine expression were observed after stimulation in vitro of purified CD4+ T cell populations obtained from HIV-infected individuals at different stages of disease. These results indicate that a switch from the TH1 to the TH2 cytokine phenotype does not occur during the progression of HIV disease.
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PMID:Lack of evidence for the dichotomy of TH1 and TH2 predominance in HIV-infected individuals. 802 39

This viewpoint proposes that an imbalance in the TH1-type and TH2-type responses contributes to the immune dysregulation associated with HIV infection, and that resistance to HIV infection and/or progression to AIDS is dependent on a TH1-->TH2 dominance. This hypothesis is based on the authors' findings that: (1) progression to AIDS is characterized by loss of IL-2- and IFN-gamma production concomitant with increases in IL-4 and IL-10; and (2) many seronegative, HIV-exposed individuals generate strong TH1-type responses to HIV antigens.
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PMID:A TH1-->TH2 switch is a critical step in the etiology of HIV infection. 839 83

Evidence has been presented for the involvement of IFN-gamma, IL-4 and TGF-beta in AIDS. Measured plasma levels may, however, poorly reflect in vivo production, since cytokines act auto- and paracrinally and have very short half life in plasma. In situ hybridization with complementary DNA oligonucleotide probes was used to enumerate blood mononuclear cells expressing cytokine messenger RNA (mRNA). HIV-infected patients had elevated blood levels of cells expressing each of the cytokines, with predominance for cells expressing TGF-beta mRNA. All AIDS patients included had elevated numbers of IL-4 mRNA-expressing cells, and levels of cells expressing this cytokine correlated inversely with counts of CD4+ cells in blood, reflecting the involvement of Th2-like cells in later stages of HIV infection. The described approach should be useful in further studies of cytokines in HIV infection and other diseases.
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PMID:Increased levels of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) mRNA expressing blood mononuclear cells in human HIV infection. 814 67

The ability of activated T lymphocytes to extravasate and reach inflammatory and malignant foci in the tissues is a basic function of cellular immunity. Recent evidence strongly suggests that the urokinase receptor (uPAR) holds a central position in the development of human two-chain urokinase-mediated pericellular proteolysis and matrix degradation, an important element in cell migration. In this report we establish uPAR as a pan T cell activation Ag. As determined by FACS analysis, CD3+ lymphocytes from healthy donors exhibited no significant uPAR expression. In contrast, patients (e.g., HIV-positive donors) showed distinct uPAR expression, confined to HLA-DR+ cells, in up to 80% of all T cells. In vitro activation by PMA caused a rapid up-regulation of membrane uPAR in all healthy donor T cells and was accompanied by enhanced receptor synthesis and elevated uPAR mRNA levels. A similar induction resulted from activation via the TCR/CD3 complex using mitogens (PHA, and Con A), anti-CD3 antibodies, and alloantigen. Receptor expression at single cell level was also modulated by a number of cytokines. IL-2, IL-4 and IL-7 increased uPAR presentation on 20 to 50% of the T cell population, and combined stimulation of bulk cultures demonstrated an additive effect of IL-2 and IL-7, whereas the response to each of the two was inhibited by IL-4. In addition, TGF-beta 1 substantially reduced the uPAR expression in T cell cultures responding to PHA, IL-2, and IL-7. Irrespective of the activating reagent, the T cells appeared to produce the same molecular uPAR species, but the affinity of uPAR expressed in PMA blasts was decreased, presumably because of a differential location at the cell surface. All activated cultures showed co-expression of uPAR and CD25. The finding that the urokinase receptor is an activation Ag may suggest that cell-associated plasminogen activation is involved in extravasation and migration of activated T cells.
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PMID:Urokinase receptor. An activation antigen in human T lymphocytes. 828 34

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. 836 71


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