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

Failure of CD4(+) T cells to proliferate in response to antigenic stimulation is a characteristic of HIV infection. Analysis of the proliferation defect has been hampered by an inability to identify CD4(+) cells with T cell receptor specificity for antigen. To focus only on cells that had been stimulated through the T cell receptor, CD4(+) T cells were stimulated with an anti-Vbeta3 Ab that activates approximately 3-5% of peripheral blood T cells. This approach revealed proliferation defects in cells from HIV-infected patients that were not appreciated using anti-CD3 Ab stimulation and provided the capacity to examine responses on a single cell basis. After anti-Vbeta3 Ab stimulation, CD4(+)Vbeta3(+) cells from HIV-infected patients demonstrated defects in expression of cell cycle-associated proteins, D-type cyclins, and cyclin A. However, the expression of early activation markers, CD69 and CD25, was not significantly impaired in cells from most patients. Thus, CD4(+) T cell proliferation failure in HIV disease is characterized by dysregulated activation that precludes cell cycle progression. This proliferation defect was most apparent in patients with diminished CD4(+) T cell numbers and higher plasma HIV RNA levels. CD4(+) T cell proliferation failure may be a key determinant of immune impairment in HIV disease.
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PMID:HIV-1 infection impairs cell cycle progression of CD4(+) T cells without affecting early activation responses. 1154 82

Depletion of CD4(+) T lymphocytes is a central immunological characteristic of HIV-1 infection. Although the mechanism of such CD4(+) cell loss following macrophage-tropic (R5) HIV-1 infection remains unclear, interactions between viral and host cell factors are thought to play an important role in the pathogenesis of HIV-1 disease. Based on the observation that TGF-beta1 enhanced expression of HIV chemokine coreceptors, the role of this host factor in virus effects was investigated using PBLs cultured in a nonmitogen-added system in the absence or presence of TGF-beta1. Most CD4 cells in such cultures had the phenotype CD25(-)CD69(-)DR(-)Ki67(-) and were CD45RO(bright)CD45RA(dim). Cultured cells had increased expression of CCR5 and CXCR4 and supported both HIV-1 entry and completion of viral reverse transcription. Virus production by cells cultured in the presence of IL-2 was inhibited by TGF-beta1, and this inhibition was accompanied by a loss of T cells from the culture and an increase in CD4(+) T cell apoptosis. Whereas R5X4 and X4 HIV-1 infection was sufficient to induce T cell apoptosis, R5 HIV-1 failed to induce apoptosis of PBLs in the absence of TGF-beta1 despite the fact that R5 HIV-1 depletes CD4(+) T cells in vivo. Increased apoptosis with HIV and TGF-beta1 was associated with reduced levels of Bcl-2 and increased expression of apoptosis-inducing factor, caspase-3, and cleavage of BID, c-IAP-1, and X-linked inhibitor of apoptosis. These results show that TGF-beta1 promotes depletion of CD4(+) T cells after R5 HIV-1 infection by inducing apoptosis and suggest that TGF-beta1 might contribute to the pathogenesis of HIV-1 infection in vivo.
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PMID:Synergistic induction of apoptosis in primary CD4(+) T cells by macrophage-tropic HIV-1 and TGF-beta1. 1154 26

Interleukin-2 has been widely used in HIV-1+ subjects as an immunoactivating agent. In this study, we investigated cytokine production, Ki67 antigen expression and the modulation of the surface phenotype of the CD4/CD25+ subset as compared to the reciprocal CD4/CD25- subset in IL-2-treated HIV+ patients. Our findings suggest that CD4 T cells are heterogeneous in responding to IL-2, because CD4/CD25+ cells sharply increased their "memory" phenotype, their Ki67 antigen expression and were the main in vivo targets for IL-2-dependent proliferation during therapy, while the percentages of IFN-gamma+ (terminally differentiated) cells remained unchanged at the end of therapy. Conversely, the CD4+/CD25- subpopulation showed an expansion of differentiated cells and a slight increase in the proliferation rate. The use of anti-retroviral therapy alone (HAART) reduced the proliferation and increased the differentiation of both CD4 subsets. Our data suggest that IL-2 has a moderate capacity to activate resting T cells in vivo and is probably unable to boost HIV-1 from latency to the replicative state.
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PMID:Effects of interleukin-2 therapy on the proliferation and differentiation of CD4/CD25 positive and CD4/CD25 negative cells in HIV+ patients. 1156 23

Heterosexual transmission of human immunodeficiency virus (HIV-1) is the predominant mode of infection world-wide. To better understand sexual transmission of HIV-1 in women we have analysed virus co-receptor and cellular activation marker expression on T lymphocyte subsets from the cervical epithelium and have made comparisons with peripheral blood T cells. Intraepithelial cervical T lymphocytes were obtained with a cytobrush, immunolabelled and analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) were found to be more highly expressed on cervical than on blood T lymphocytes. These higher levels of activation on cervical T lymphocyte subsets could facilitate HIV-1 infection. CXCR4 was expressed at marginally higher levels than CCR5 on T cells from the cervical epithelium and peripheral blood. Thus, the preferential transmission of macrophage tropic strains of HIV-1 following sexual contact cannot be explained solely on the expression of chemokine co-receptors by T lymphocyte subsets.
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PMID:Higher levels of activation markers and chemokine receptors on T lymphocytes in the cervix than peripheral blood of normal healthy women. 1160 Jan 81

Gammadelta T lymphocytes recognize nonpeptidic microbial antigens without MHC restriction and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. This innate recognition involves both T Cell Receptor (TCR) and NK-receptor mediated signalling through non-peptidic metabolites and HLA class I down-regulation. We observed that HLA-masking and nonpeptidic phosphoantigens induce the expression of CD25 and CD69 activation markers on the surface of gammadelta T cells. Interestingly, CD94+ cell depletion by magnetic beads showed that the expression of this antigen is essential for Vdelta2 T cell activation by HLA-masking. Moreover, both phosphoantigen-stimulation and in vitro HIV infection resulted in marked Vgamma9Vdelta2 T cell expansion, whereas HLA-masking was unable to induce proliferative responses. Finally, we observed a relevant hyporesponsiveness to non-peptidic antigens in HIV-infected persons and in cord blood cells from healthy donors when compared to adult PBMC from uninfected donors. Altogether, the reduced ability to naturally recognize the infected cells may contribute to HIV-disease progression and may facilitate maternal transmission of HIV infections.
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PMID:Antiviral activity and anergy of gammadeltaT lymphocytes in cord blood and immuno-compromised host. 1169 34

To determine whether viral load rebounds during HAART impact on CD4+ T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4+ T cell count was 0.32 cell/mm3/day in group 1 and only 0.14 cell/mm3/day in group 2 (P < 0.0001). However, the patterns of changes in CD4+ and CD8+ T cell subsets during therapy were very similar across the two groups with only subtle and very limited differences. We conclude that permanent control of HIV replication could be necessary for faster immune reconstitution.
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PMID:CD4 T cell recovery is slower in patients experiencing viral load rebounds during HAART. 1170 74

IL-16 is a multi-functional cytokine that uses CD4 as a receptor to signal diverse biological activities by target cells including T-lymphocytes, monocytes and eosinophils. IL-16 has been shown to repress HIV-1 infection in lymphocytes and monocytic cells and it is active against both laboratory and naturally acquired virus isolates. In lymphocytes, the repressive effect of IL-16 occurs at the level of virus transcription, while it appears to inhibit viral entry in monocytic cells. Clinical studies comparing serum IL-16 levels with the state of HIV-1 disease suggest that this cytokine is a functionally significant endogenous antiviral factor. The antiviral activity of IL-16 may be of therapeutic benefit in HIV/AIDS but its greatest potential is for immune reconstitution. Stimulation of CD4+ T-cells with IL-16 primes cells to respond to IL-2, by upregulating the expression of IL-2 receptor p75 (CD25). Co-treatment of peripheral blood mononuclear cells (PBMC) with IL-16 plus IL-2 (or IL-15) in vitro selectively expands the population of CD4+ T-cells. Clinical trials of recombinant IL-2 have already shown promise in HIV/AIDS. In combination with IL-16, the beneficial effects of IL-2 may be augmented and specifically targeted to CD4+ T-cells. Thus, IL-16 shows considerable promise as an agent for the biological therapy of HIV/AIDS.
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PMID:Prospects for IL-16 in the treatment of AIDS. 1172 16

The macaque-simian immunodeficiency virus (SIV) system is one of the best animal models available to study the role of dendritic cells (DCs) in transmission and pathogenesis of HIV, as well as to test DC-based vaccine and therapeutic strategies. To better define and optimize this system, the responsiveness of macaque monocyte-derived DCs to a variety of maturation stimuli was examined. Characteristic immunophenotypic and functional DC maturation induced by standard monocyte conditioned medium (MCM) was compared to the activation induced by a panel of stimuli including soluble CD40L, LPS, Poly I:C, PGE(2)/TNFalpha, and a cocktail mixture of PGE(2)/TNFalpha/IL-1beta/IL-6. Immunophenotypic analysis confirmed that all stimuli induced stable up-regulation of CD25, CD40, CD80, CD83, CD86, HLA-DR, DC-LAMP (CD208), and DEC-205 (CD205). In general, macaque DCs exhibited weaker responses to LPS and Poly I:C than human DCs, and soluble CD40L stimulation induced variable expression of CD25. Interestingly, while the endocytic capacity of CD40L-matured cells was down-modulated comparably to DCs matured with MCM or the cocktail, the T cell stimulatory activity was not enhanced to the same extent. The particularly reproducible and potent T cell stimulatory capacity of cocktail-treated DCs correlated with a more homogenous mature DC phenotype, consistently high levels of IL-12 production, and better viability upon reculture compared to DCs activated by other stimuli. Furthermore, cocktail-matured DCs efficiently captured and presented inactivated SIV to SIV-primed T cells in vitro. Thus, the cocktail represents a particularly potent and useful stimulus for the generation of efficacious immunostimulatory macaque DCs.
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PMID:Enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of SIV-specific T cell responses. 1179 91

Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the predominant mode of infection worldwide. Increased risk of HIV-1 transmission has been reported with oral contraceptive use. To elucidate the underlying mechanism of this observation, intraepithelial endocervical T lymphocytes from women using oral contraceptives were analysed for expression of activation and chemokine receptors. T lymphocytes from the cervical epithelium and peripheral blood of women using combined oral contraceptives (COC) and those using no contraceptive method (NONE) were compared. Cervical T lymphocytes were obtained with a cytobrush and in parallel, mononuclear leukocytes were separated from blood by centrifugation over a ficoll-hypaque gradient. Cellular activation markers and HIV-1 chemokine co-receptors, CXCR4 and CCR5, were analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) on T cells were expressed at higher levels in the cervical epithelium than peripheral blood T cells but were no different in those women using COC. CXCR4 was widely expressed on cervical and on blood T cells, but was not influenced by COC use. By contrast, the number of T cells expressing CCR5 increased in women using COC (P<0.05). The level of cervical CCR5 expression per cell was shown to increase on both activated CD4(+) (CD69(+), P<0.05; HLA-DR(+), P<0.01) and CD8(+) (CD69(+), P<0.05; HLA-DR(+), P<0.05) T lymphocytes compared with COC use. These data show that with COC use, the expression of CCR5 on CD4(+) T lymphocytes is increased. Furthermore, the cell surface density of CCR5 is increased on both CD4(+) and CD8(+) T lymphocyte subsets. These findings suggest a mechanism by which oral contraceptive use can increase the risk of HIV-1 transmission.
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PMID:Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women. 1183 99

In 40 HIV-infected children, 8-10 years old, belonging to the category A state of infection, the following flow-cytometric parameters were scored: percentage levels of different blood lymphocytes; surface expression of some activation and memory markers in CD4+ cells; switch to Th1 or Th2 of in vitro -stimulated CD4+ cell, tested by intracellular production of interleukin-2 or interleukin-4. Each investigation was carried out both before and 3 months after antiretroviral therapy (AZT and ddC). Some post-therapy changes concerning blood lymphocyte percentages were noticed, not only within CD4+ subpopulation, but also within CD8+, HLA-DR+/CD3 (T-activated) and CD16+CD56+ cells, respectively. On the other hand, following antiretroviral treatment, in HIV- originated CD4+ fresh cells, an improvement of pre-therapy increased values of surface activation (CD69, CD25) markers on memory (CD45RO+) cells, as well as of pre-therapy reduced rate of switching to Th1, revealed by intracellular interleukin-2 synthesis, was found. The significance of data obtained in the multi-way immune monitoring of antiretroviral therapy, in pediatric AIDS, as an additional investigation panel, is discussed.
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PMID:Multi-way flow cytometric immune monitoring of antiretroviral therapy in HIV-infected children. 1184 33


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