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

Previously we demonstrated an inhibitory effect of interleukin-4 (IL-4) on establishment of human immunodeficiency virus type 1 (HIV-1) infection in primary macrophages. The reported similarities between the biological effects of IL-4 and IL-10 prompted us to study the effect of IL-10 on HIV-1 replication. Treatment of primary macrophages with IL-10 resulted in inhibition of HIV-1 infection. This inhibitory effect was specific for macrophages, since IL-10 did not interfere with HIV-1 replication in primary T cells. Semiquantitative PCR analysis excluded an inhibitory effect of IL-10 on virus entry and reverse transcription. Effects of IL-10 on HIV-1 long terminal repeat-driven chloramphenicol acetyltransferase activity also could not be demonstrated in a transient expression system in primary derived macrophages. In agreement with this, Northern (RNA) blot analysis demonstrated equal amounts of viral RNA species irrespective of IL-10 treatment, also excluding an inhibitory effect on elongation of virus transcription. Monocyte-derived macrophages (MDM) treated with IL-10 after HIV-1 inoculation showed accumulation of apparently mature p24 protein suggestive of an inhibitory effect at the level of virus assembly. IL-10 treatment of MDM prior to HIV-1 inoculation did not result in accumulation of p24 protein. Immunoblot analysis indeed showed the absence of mature p24 and gp120 but accumulation of the Pr53 gag-encoded protein in HIV-1-inoculated, IL-10-pretreated MDM, suggesting an inhibitory effect at the level of protein processing. A combination of IL-4 and IL-10 resulted in a cumulative inhibitory effect on HIV-1 replication in MDM. The recent observation that in the course of HIV-1 infection a shift occurs in the production of IL-2/gamma interferon toward enhanced IL-4 and IL-10 production and the reported shift from preferential macrophage-tropic towards preferential T-cell-tropic HIV-1 variants with progression of disease suggest that cytokines have an important role in the in vivo regulation of HIV-1 tropism.
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PMID:Interference of interleukin-10 with human immunodeficiency virus type 1 replication in primary monocyte-derived macrophages. 793 78

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

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

The loss of T helper cell (TH) function in asymptomatic HIV type 1-infected individuals occurs before the decline in CD4+ T cells. At least part of the loss in TH function results from changes in immunoregulatory cytokine profiles. To investigate the role of IL-10 in such dysregulation, we tested whether: (a) expression of IL-10-specific mRNA would be upregulated in PBMC from asymptomatic, HIV-infected (HIV+) individuals; (b) PBMC from these same individuals would produce increased levels of IL-10 when stimulated in vitro with phytohemagglutinin; and (c) defective antigen-specific TH function could be restored by anti-IL-10 antibody. We observed that IL-10-specific mRNA was marginally upregulated, and increased levels of IL-10 were produced by PBMC from HIV+ individuals compared with PBMC from uninfected individuals. Those individuals whose TH function was more severely compromised produced higher levels of IL-10. Additionally, defective antigen-specific TH function in vitro could be reversed by anti-IL-10 antibody, including the response to HIV envelope synthetic peptides. Furthermore, the antigen-specific TH responses of HIV-uninfected PBMC could be reduced with IL-10, a process reversed by anti-IL-10. These results confirm that the early loss of TH function in HIV+ individuals is due at least in part to cytokine-induced immune dysregulation, and support the hypothesis of a switch from a predominant type 1 state to a predominant type 2 condition in HIV infection.
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PMID:Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus. 811 10

Given the dissemination of acquired immunodeficiency syndrome (AIDS) in Latin America, where Chagas' disease is endemic, there is a present and increasing risk of concurrent infections with human immunodeficiency virus (HIV) and Trypanosoma cruzi. We used the model of murine acquired immunodeficiency syndrome (MAIDS) caused by a murine leukemia virus (MuLV) that induces immunologic alterations with similarities to those accompanying human HIV infection to study aspects of concomitant infections. The MuLV infection was found to reactivate T. cruzi infection in C57Bl/10 mice, as indicated by elevated parasitemia and lymphocytic infiltration in the myocardium. The T cells from these animals did not respond to T. cruzi antigens (lymphocyte proliferation, interferon-gamma, or interleukin-2 [IL-2] production) but had increased levels of IL-10. Trypanosoma cruzi-specific antibody was decreased but not absent in dually infected animals. In a second set of experiments, we infected MAIDS-resistant B6D2 mice with MuLV, followed by infection with T. cruzi. These animals had higher parasitemia than those infected with T. cruzi alone. More interestingly, only dually infected animals developed MAIDS. The present report describes the activation of T. cruzi infection by MuLV as well as the aggravation of MuLV infection by T. cruzi. These results may be relevant to coinfections with retrovirus and protozoan parasites in humans.
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PMID:Aggravation of both Trypanosoma cruzi and murine leukemia virus by concomitant infections. 825 98

Because cytokines have a central role in the regulation and function of the human immune system, expression of several key cytokine genes in HIV infection was compared by quantitative polymerase chain reaction studies in lymphocytes from HIV-seronegative and -seropositive subjects. Elevated levels of IFN-gamma mRNA and lowered IL-2 mRNA were found in the PBMC of eight seropositive men with CD4 T cells over 500/mm3 (mean, 647/mm3), whereas IL-4 and IL-10 mRNA were not changed significantly. PBMC obtained 2 yr later from four of these patients with stable disease status (unchanged CD4 T cell number) showed median mRNA levels that were nearer normal for IFN-gamma and for IL-2. Four other men whose CD4 levels fell more than 200/mm3 in the following 2 yr, however, showed increased IFN-gamma and lowered IL-2. Purified CD4 and CD8 T cells from 10 HIV-seropositive and 10 -seronegative homosexual men were compared. Cytokine gene expression was found to be markedly different in CD4 and CD8 T cells from HIV-seropositive men. In CD8 T cells on a per-cell basis, the levels of cytokine mRNA were substantially lower than in CD4 T cells and were not markedly changed in HIV infection. In the CD4 T cells, on a per-cell basis, the mean mRNA levels of IFN-gamma, IL-10, and TNF-alpha were increased substantially (p < 0.001) in HIV infection. IL-2 gene expression was not increased significantly. Thus, the low IL-2 mRNA expression seen in PBMC is primarily due to the reduced CD4 T cell numbers. Increased expression of IFN-gamma genes in CD4 T cells, however, indicates that these cells may be responsible for substantial amounts of circulating IFN-gamma that occur in HIV infection. The striking difference in the effect of HIV infection on the expression of IFN-gamma and IL-2 genes indicates that these cytokines are under separate control. IL-4 mRNA levels were not changed. IL-10 gene expression, however, was increased more in early HIV infection, with less of an increase later. Expression of all cytokines in CD4 T cells appeared to subside late in HIV infection. However, the balance of cytokine expression was altered in all stages of HIV infection.
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PMID:Elevated IFN-gamma and decreased IL-2 gene expression are associated with HIV infection. 840 54

The injection of DBA/2 parental lymphocytes into adult, immunologically intact (C57BL/6 x DBA/2) F1 hybrid mice results in a chronic graft-vs-host reaction (GVHR) characterized by a deficiency in CD4+ T cell functions and a B cell activation leading to autoantibody production. The discovery that distinct subpopulations of Th cells may regulate the effector immune functions led us to investigate whether the chronic GVHR differentially affects Th subsets. Data are presented indicating that mice undergoing a GVHR spontaneously produced lymphokines of Th2 origin. IL-4 and IL-10 mRNA were detected in the spleens of GVH mice, and IL-4 was shown to be responsible for the increased expression of class II Ag on B cells. Moreover, upon polyclonal activation in vitro, GVH T cells exhibited defective IL-2 and IFN-gamma production but elevated IL-4 production. We conclude that the chronic GVHR is characterized by a selective deficiency in cells secreting IL-2 and IFN-gamma and a hyperactivation of Th2 cells. The simultaneous production of IL-4 and IL-10 might explain the association between B cell hyperactivity and impairment of Th1-like activities in various models that associate autoimmunity and immunosuppression, such as GVHR and HIV infection.
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PMID:Preferential activation of Th2 cells in chronic graft-versus-host reaction. 841 69

The severe depletion of CD4+ T cells is the most obvious and dramatic immunologic event that occurs in individuals infected with the human immunodeficiency virus (HIV) type 1 during development to AIDS. Nevertheless, a complex and sequential pattern of loss of T-helper cell (TH) function can occur years before development of AIDS symptoms. Such suppression could be due to immunosuppressive factors that are either products of HIV, such as gp120 and tat, or HIV-induced immunoregulatory cytokines such as transforming growth factor-beta and IL-10. Recent data suggest that multiple and independent immunosuppressive factors, including gp120-induced suppression and IL-10, are responsible for the loss of TH function seen in HIV-infected individuals before development of symptoms. The same TH functional abnormalities observed in adult patients are also seen in pediatric cases. Pediatric cases of HIV infection present some unique problems, however, in that one needs to be able to distinguish between HIV-induced suppression of TH function and the absence of TH function that is due to lack of maturation or immunologic priming.
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PMID:Abnormalities of immune regulation in human immunodeficiency virus infection. 843 78


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