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

Different features have been associated with low susceptibility to HIV type 1 (HIV-1) infection in exposed seronegative individuals. These include genetic make-up such as homozygosity for the CCR5-Delta32 allele and the presence of HIV-specific CTLs. We studied immune activation and immune responsiveness in relation to HIV-1 susceptibility in 42 high-risk seronegative (HRSN) participants of the Amsterdam Cohort Studies and 54 men from the same cohort who were seronegative at the moment of analysis but later became HIV seropositive. HRSN had higher naive (CD45RO CD27) CD4 and CD8 T cell numbers and lower percentages of activated (HLADR CD38, CD70) CD4 and proliferating (Ki67) CD4 and CD8 T cells, irrespective of previous episodes of sexually transmittable infections. Furthermore, whole blood cultures from HRSN showed lower lymphoproliferative responses than healthy laboratory controls. These data suggest that low levels of immune activation and low T cell responsiveness may contribute to low HIV susceptibility.
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PMID:Low-level CD4+ T cell activation is associated with low susceptibility to HIV-1 infection. 1623 8

The human immunodeficiency virus (HIV)-mediated immune response may be beneficial or harmful, depending on the balance between expansion of HIV-specific T cells and the level of generalized immune activation. The current study utilizes multicolor cytokine flow cytometry to study HIV-specific T cells and T-cell activation in 179 chronically infected individuals at various stages of HIV disease, including those with low-level viremia in the absence of therapy ("controllers"), low-level drug-resistant viremia in the presence of therapy (partial controllers on antiretroviral therapy [PCAT]), and high-level viremia ("noncontrollers"). Compared to noncontrollers, controllers exhibited higher frequencies of HIV-specific interleukin-2-positive gamma interferon-positive (IL-2(+) IFN-gamma(+)) CD4(+) T cells. The presence of HIV-specific CD4(+) IL-2(+) T cells was associated with low levels of proliferating T cells within the less-differentiated T-cell subpopulations (defined by CD45RA, CCR7, CD27, and CD28). Despite prior history of progressive disease, PCAT patients exhibited many immunologic characteristics seen in controllers, including high frequencies of IL-2(+) IFN-gamma(+) CD4(+) T cells. Measures of immune activation were lower in all CD8(+) T-cell subsets in controllers and PCAT compared to noncontrollers. Thus, control of HIV replication is associated with high levels of HIV-specific IL-2(+) and IFN-gamma(+) CD4(+) T cells and low levels of T-cell activation. This immunologic state is one where the host responds to HIV by expanding but not exhausting HIV-specific T cells while maintaining a relatively quiescent immune system. Despite a history of advanced HIV disease, a subset of individuals with multidrug-resistant HIV exhibit an immunologic profile comparable to that of controllers, suggesting that functional immunity can be reconstituted with partially suppressive highly active antiretroviral therapy.
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PMID:Phenotypic, functional, and kinetic parameters associated with apparent T-cell control of human immunodeficiency virus replication in individuals with and without antiretroviral treatment. 1625 52

HIV-1 infection generates maturational responses in overall CD4 and CD8 T cell populations in adults, with elevated expression of lytic effector molecules perforin and granzyme B, and reduced expression of CCR7 and CD45RA. Here, we have found that these marked effects were significantly less pronounced in children, both in terms of the skewed CCR7/CD45RA expression profile as well as the increased perforin expression. Similar to adults, HIV-specific CD8 cells in children were largely CD27+ CD45RA- and lacked perforin. However, one pediatric subject with late-stage infection displayed robust expansion of Gag 77-85-specific CD8 T cells which were perforin+ and lytic, but lacked expression of CD27 and IFNgamma. Our data indicate that the T cell effector maturation induced by HIV-1 infection is markedly weaker in children as compared to adults. The data also suggest, however, that the perforin-deficient state of HIV-specific CD8 T cells in children may be reversible.
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PMID:CD8 T cell effector maturation in HIV-1-infected children. 1640 47

HIV infection activates abnormally the immune system and the chronic phase is accompanied by marked alterations in the CD8 compartment. The expression of CD127 (IL-7R alpha chain) by memory CD8 T lymphocytes in HIV-infected patients is analysed and reported. The memory CD8 T cell subset was characterized by expression of CD45RA and CD27 markers, and CD127 cell surface expression was measured ex vivo by four-colour flow cytometry. HIV infection was associated with a fall in the proportion of CD127(+) cells among memory CD8 lymphocytes that resulted in a higher CD127(-) CD45RA(-)CD27(+) CD8 T cell count in HIV-infected patients. Diminished CD127 cell surface expression [mean fluorescence intensity (MFI)] by positive cells was also observed in this subset. The data suggest that these defects were reversed by highly active anti-retroviral therapy (HAART). The regulation of CD127 expression was also studied in vitro. Down-regulation of CD127 by interleukin (IL)-7 was observed in memory CD8 lymphocytes from healthy donors and HAART patients. Expression of CD127 by memory CD8 lymphocytes cultured in the absence of IL-7 confirmed that IL-7R regulation is altered in viraemic patients. Under the same experimental conditions, memory CD8 lymphocytes from HAART patients were shown to express CD127 at levels comparable to cells from healthy individuals. Altered CD127 cell surface expression and defective CD127 regulation in the memory CD8 T lymphocytes of HIV-infected patients are potential mechanisms by which these cells may be impeded in their physiological response to endogenous IL-7 stimulatory signals. Our data suggest that these defects are reversed during the immune reconstitution that follows HAART.
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PMID:CD127 expression and regulation are altered in the memory CD8 T cells of HIV-infected patients--reversal by highly active anti-retroviral therapy (HAART). 1648 37

As interferon-gamma (IFN-gamma) is produced at lower levels by neonatal than adult T cells, we determined whether IFN-gamma influences HIV-1 replication in thymocytes. IFN-gamma significantly decreased replication of R5 but not X4 viruses, and reduced depletion of CD3(hi)CD27 (mature) thymocytes, the preferential targets for R5 HIV-1. Thus infection and depletion of functionally mature thymocytes that can produce endogenous IFN-gamma may mutually contribute to HIV-1 replication in the thymus and to reduced T-cell output.
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PMID:Interferon-gamma decreases replication of primary R5 HIV-1 isolates in thymocytes. 1654 83

While the detrimental consequences of opportunistic tuberculosis (TB) in the course and outcome of HIV-1 infection are well studied, little information about the impact of the mycobacterial infection on the phenotype of T lymphocytes is available. In this study we analyzed by cytofluorimetry the peripheral blood T cell phenotype of 13 patients with AIDS, 23 HIV-1 negative patients with active pulmonary TB, nine HIV-1/Mycobacterium tuberculosis coinfected individuals, and 21 age- and sex-matched healthy controls. CD4+ T cells were equally depleted in AIDS and coinfection (P<0.001). The findings suggest a rescuing effect of the added mycobacterial infection. CD3 T cell loss was not observed in coinfection, whereas it was severe in AIDS (P<0.001). Similar (albeit less striking) effects were observed with other markers (CD45RA, CD45RO, and CD27) that were diminished in CD4+ T cells of AIDS patients. Apparent detrimental effects of the added mycobacterial infection were the increased expression of the proapoptotic molecule CD95 on CD4+ T cells, and decreased expression of the major costimulatory molecule CD28 on CD8+ T cells. In this work we show that M. tuberculosis infection modifies the T cell phenotype of the HIV-1 infected individual.
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PMID:Impact of opportunistic Mycobacterium tuberculosis infection on the phenotype of peripheral blood T cells of AIDS patients. 1672 21

HIV-infected patients fail to fully recover cell-mediated immunity despite HAART. To identify regulatory factors, we studied the phenotype and function of in vitro cytomegalovirus (CMV)-stimulated T cells from HAART recipients. CFSE-measured proliferation showed CD4+ and CD8+ cells dividing in CMV-stimulated cultures. Compared with healthy controls, CMV-stimulated lymphocytes from HAART recipients had lower 3H-thymidine incorporation; lower IFNgamma and TNFalpha production; higher CD4+ CD27- CD28- and CD8+ CD27- CD28- frequencies; lower CD4+ CD25hi; and higher FoxP3 expression in CD8+ CD25hi cells. CMV-specific proliferation correlated with higher IFNgamma, TNFalpha and IL10 levels and higher CD4+ perforin+ and CD8+ perforin+ frequencies. Decreased proliferation correlated with higher CD4+ CD27- CD28- frequencies and TGFbeta1 production, which also correlated with each other. Anti-TGFbeta1 neutralizing antibodies restored CMV-specific proliferation in a dose-dependent fashion. In HIV-infected subjects, decreased proliferation correlated with higher CMV-stimulated CD8+ CD25hi frequencies and their FoxP3 expression. These data indicate that FoxP3- and TGFbeta1-expressing regulatory T cells contribute to decreased immunity in HAART recipients.
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PMID:Regulatory T cells generated during cytomegalovirus in vitro stimulation of mononuclear cells from HIV-infected individuals on HAART correlate with decreased lymphocyte proliferation. 1678 63

Human immunodeficiency virus type 1 (HIV-1) replication depends on CD4 and coreceptor expression as well as host factors associated with the activation state of the cell. To determine the impact of the activation stage of thymocytes on the HIV-1 life cycle, we investigated R5 and X4 HIV-1 entry, reverse transcription, and expression in discrete thymocyte subsets at different stages of T-cell development. Early after infection, preferential entry and replication of R5 HIV-1 were predominantly detected in mature CD3(+/hi) CD27(+) thymocytes. Thus, R5 HIV-1 targets the stage of development where thymocytes acquire functional responsiveness, which has important implications for HIV pathogenesis. In contrast, X4 HIV-1 expression and replication were primarily found in immature CD3(-/+/low) CD27(-) CD69(-) thymocytes. HIV-1 proviral burden and virus expression in thymocyte subsets correlated with the expression of the highest levels of the respective coreceptor. R5 and X4 HIV-1 entered and completed reverse transcription in all subsets tested, indicating that the activation state of thymocytes and coreceptor expression are sufficient to support full reverse transcription throughout development. Although R5 HIV-1 is expressed mainly in mature CD3(+/hi) CD27(+) thymocytes, 5.3% of HIV-1-infected immature thymocytes express R5 HIV-1, indicating that potentially latent viral DNA can be established early in T-cell development.
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PMID:Human immunodeficiency virus persistence and production in T-cell development. 1698 9

The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8+ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis strain expressing human immunodeficiency virus type 1 (HIV-1) gp120-elicited CD4+ T lymphocytes with a functional profile of helper cells as well as a CD8+ T-lymphocyte population. These CD8+ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant-mycobacterium-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 Env to gp120-specific CD8+ T lymphocytes. This work demonstrates a remarkable skewing of recombinant-mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8+ T cells and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.
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PMID:Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis. 1705 Jun 8

The failure of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells to control chronic HIV-1 infection could be due to the progressive loss of their capacities to undergo normal memory effector differentiation. We characterized and compared the expressions of CD27, CD28, CD57, and CD62L by Epstein-Barr virus (EBV)-, cytomegalovirus (CMV)-, and HIV-1-specific CD8+ T cells by six-color, eight-parameter flow cytometry. In contrast to the maturation of EBV- and CMV-specific memory CD8+ T cells, we found that HIV-1-specific CD8+ T cells did not display coordinated down-regulation of CD27 and up-regulation of CD57 and accumulated in an atypical CD27(high) CD57(low) subset. Moreover, the accumulation of CD27(high) CD57(low) HIV-1-specific CD8+ T cells was positively correlated with HIV-1 plasma viremia. The differentiation of HIV-1-specific CD8+ T cells to an effector subset is therefore impaired during chronic HIV-1 infection. This lack of normal CD8+ T-cell differentiation could contribute to the failure of cellular immune control of HIV-1 infection.
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PMID:CD27 and CD57 expression reveals atypical differentiation of human immunodeficiency virus type 1-specific memory CD8+ T cells. 1707 36


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