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

HIV and hepatis C virus (HCV) coinfection is frequently associated with rapid progression of HCV-related disease, resulting in a higher risk of cirrhosis. Data suggest that natural T cells expressing the Vdelta1 T cell receptor rearrangement are recruited in the liver of chronically HCV-infected patients and are increased in the peripheral blood of HIV-infected persons. We studied gammadelta T cell distribution in the peripheral blood and liver of HCV-infected and HIV/HCV-coinfected patients in the presence and absence of antiretroviral therapy. We observed that Vdelta1+ T cells releasing helper T cell type 1 cytokines are compartmentalized not only in the liver of HCV+ patients, but also of HIV/HCV-coinfected persons. HIV/HCV patients showed an increased frequency of both peripheral and intrahepatic Vdelta1 natural T lymphocytes, resulting in a higher degree of hepatic inflammation when compared with patients with other liver diseases. Finally, highly active antiretroviral therapy (HAART) was unable to restore Vdelta1T cell circulation to normal levels in chronically HIV-infected persons. We conclude that gammadelta T lymphocytes released from tissue to the bloodstream circulation under the influence of chronic HIV infection may contribute to intrahepatic Vdelta1 compartmentalization and progression of liver disease, independently of HAART.
AIDS Res Hum Retroviruses 2001 Sep 20
PMID:Gammadelta T cell activation by chronic HIV infection may contribute to intrahepatic vdelta1 compartmentalization and hepatitis C virus disease progression independent of highly active antiretroviral therapy. 1160 46

The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define the etiology of the enlargement, the thymuses of two HIV-infected individuals on HAART were biopsied. For more than 3 years before initiation of HAART, both patients (38 and 41 years of age) had documented CD4+ T lymphopenia. Peripheral blood samples were obtained to assess circulating CD4+ CD45RA+ CD62L+ T cells, which were thought to have recently developed in the thymus. Peripheral blood T cells from both patients and thymocytes from the second patient were also tested for levels of DNA episomes formed during T cell receptor gene rearrangement (T cell receptor rearrangement excision circles, TRECs). With HAART, peripheral blood CD4+ T cell counts increased from approximately 60/mm(3) to 552/mm(3) and 750/mm(3) for patients 1 and 2, respectively. Thymic biopsies from both patients showed normal thymus histology with active thymopoiesis. Percentages of peripheral blood CD4+ CD45RA+ CD62L+ T cells and quantitation of T cell TRECs also reflected active thymopoiesis in both patients. Thus, in these two HIV-seropositive adults examined after initiation of HAART, thymic enlargement represented active thymopoiesis. Thymopoiesis in adult AIDS patients may contribute to immune reconstitution even after prolonged CD4+ T lymphopenia.
AIDS Res Hum Retroviruses 2001 Nov 20
PMID:Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy. 1177 51

In this study, changes in plasma virus load, peripheral blood CD4 T cell counts and the T cell repertoire were assessed in eight chronically HIV-infected individuals suspending antiretroviral therapy. Despite rapid increases in virus load and substantial CD4 T cell losses during treatment interruption, no marked changes in the T cell receptor beta chain repertoire were observed. The magnitude of associated T cell repertoire perturbation thus contrasts with that observed during primary HIV infection.
AIDS 2002 Jan 25
PMID:The T cell receptor V beta repertoire shows little change during treatment interruption-related viral rebound in chronic HIV infection. 1180 14

The peripheral T cell pool is damaged by HIV-1 infection and can be regenerated by production of new T lymphocytes either from the thymus or from proliferation of post-thymic T cells. A critical question for AIDS patients is whether treatment with antiretroviral drugs can restore the capability to produce new T lymphocytes. The development of a new assay of thymus function in adults (the measurement of T cell receptor excision circles, TRECs), and studies of thymus biopsies in untreated and treated HIV-1-infected patients, have suggested that in select patients the thymus can regenerate on antiretroviral therapy. New strategies to overcome the thymic atrophy of aging are needed to improve thymic function in the majority of AIDS patients.
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PMID:Immune reconstitution in patients with HIV infection. 1181 74

Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others.
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PMID:Reactive oxygen species differentially affect T cell receptor-signaling pathways. 1191 64

The CD4 molecule functions to enhance T cell activation when it is co-aggregated with the T cell receptor for antigen (TCR) by MHC class II antigenic peptide complexes. However, independent ligation of CD4 has been shown to negatively effect signaling through the TCR in vitro. The interaction between the HIV-1 envelope glycoprotein gp120 and CD4 is a central event in the pathogenesis of AIDS and may contribute to immune deficiency via both direct and indirect mechanisms, including lytic infection of T cells and induction of CD4 signaling events resulting in apoptosis and anergy. Analysis of the consequences of interactions between CD4 and gp120 have yielded contradictory results presumably because most of these studies have focused on T cell clones of questionable relevance to the in vivo target of the virus. Here, we analyzed the effects of CD4 ligation on freshly isolated cells of human CD4 transgenic mice, and show that huCD4 preligation, in the absence of human CXCR4, has an inhibitory effect on both early and late T cell activation events. CD4 signaling negatively regulates the response to antigen, as well as to anti-TCR mAb. In addition, we show here that this negative signal requires the cytoplasmic tail of CD4. These results suggest that in HIV infected patients the interaction of gp120 with CD4 induces unresponsiveness of CD4+ T cells to subsequent activation by antigen.
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PMID:Ligation of human CD4 interferes with antigen-induced activation of primary T cells. 1200 44

It is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long-term non-progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV-LTNP population (P < 0.05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu-lation. At follow up (1-2 years later), those patients in which CD4 levels were below 500 x 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (gammadelta) T cell receptor and CD8 were also seen in the HIV-LTNP patients compared with controls (P = 0.002). The increase in CD8+ T cells in the HIV-LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in gammadeltaT cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection.
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PMID:T cell receptor usage in patients with non-progressing HIV infection. 1229 61

LP-BM5 murine leukemia virus (MuLV) infection causes murine acquired immunodeficiency syndrome (MAIDS), a disease characterized by varied functional abnormalities of immunocompetent cells. We found that MAIDS progression was severely retarded in IL-15 transgenic (Tg) mice constructed with cDNA encoding secretable IL-15 under the control of an MHC class I promoter. Several immune defects, including impaired natural killer activity, depressed IFN-gamma production by T cells stimulated with anti-T cell receptor cross-linking, and increased susceptibility to Mycobacterium bovis infection, were prevented in IL-15 Tg mice inoculated with LP-BM5 MuLV. Cytotoxic T lymphocyte response to a highly antigenic 10-mer peptide encoded by LP-BM5-defective virus gag p12 gene was detected in the spleen and peritoneal exudate cells from IL-15 Tg mice infected with LP-BM5 MuLV. Intramuscular injection of cDNA encoding secretable IL-15 also prevented the development of MAIDS. These results indicate that IL-15 prevents the progression of MAIDS and may provide insight into an immunotherapeutic approach using the IL-15 gene for controlling retrovirus-induced immunodeficiency.
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PMID:Overexpression of interleukin-15 prevents the development of murine retrovirus-induced acquired immunodeficiency syndrome. 1240 18

In this study, we sought to characterize the T lymphocyte recovery in vertically HIV-1-infected children who respond to long-term highly active antiretroviral therapy (HAART). A 3-year longitudinal retrospective study was used to perform a cross-sectional study of 32 children rated according to the time course of CD4(+) T cell percentages in response to antiretroviral therapy and CDC clinical classification: (1) long-term asymptomatic (LTA group): 8 children in A1 during the whole follow-up period; (2) responsive to HAART (Rec group): 13 children in C3 before HAART who achieved CD4(+) T cell counts of > 500 cells/mm(3) after 3 years of HAART; and (3) nonresponsive to HAART (Non-Rec group): 11 children in C3 during the whole follow-up period despite 3 years of HAART. We also studied 17 healthy age-matched uninfected children as controls. Lymphoproliferative responses (LPRs) were evaluated by incorporation of [(3)H]thymidine, identification of T cell subsets by three-color flow cytometry, and determination of thymic production of T cells by quantification of T cell receptor rearrangement excision circles (TRECs). Interestingly, the Rec group showed an increase in percentage of CD4(+) T cells and a decrease in viral load, and recovered LPRs to mitogens and recall antigens, with values similar to those of the LTA group. Moreover, the Rec group produced similar percentages and absolute counts of naive (CD45RA(+)CD62L(+)) CD4(+) and CD8(+) T cells, and TRECs similar to those of the LTA group. In particular, the Rec group produced similar percentages of CD8(+)CD28(-)CD57(+) and CD8(+)CD28(-)CD57(-) T cell subsets compared with controls. Our data indicate that among children who have already progressed to AIDS and severe immunodeficiency but who respond to HAART, the immune system can recover and resemble those of nonprogressors or even uninfected children, in quantitative as well as in functional terms.
AIDS Res Hum Retroviruses 2002 Dec 10
PMID:Characterizing immune reconstitution after long-term highly active antiretroviral therapy in pediatric AIDS. 1248 11

Circulating Vgamma2/Vdelta2(+) T cells, normally constituting 3-6% of all CD3(+) T cells in blood, are severely depleted after HIV infection. The mechanism(s) for Vgamma2/Vdelta2(+) T cell depletion are unknown, partly because these cells are CD4(-) and resistant to HIV infection. To determine whether this cell depletion was general for all Vgamma2(+) cells or specific for an individual subset, we analyzed the Vgamma2 repertoire and found consistent differences between HIV(+) and uninfected control samples. The change in Vgamma2 repertoire was the result of preferentially depleting only those Vgamma2 cells that express the Jgamma1.2 segment. The specific loss of Vgamma2-Jgamma1.2(+) cells was polyclonal, as the Vgamma subset retained normal diversity even after HIV infection, and loss occurred without significant changes in the paired chain (Vdelta2) repertoire, or in the alternate Vdelta1 chain repertoire. Specific depletion of Vgamma2-Jgamma1.2/Vdelta2 T cells is the first evidence of a common, T cell receptor-dependent cell loss in HIV disease and it provides a clear example of bystander cell depletion. Vgamma2-Jgamma1.2/Vdelta2 T cells mediate potent responses to microbial pathogens including HIV, and loss of this subset is an important aspect of AIDS pathogenesis.
AIDS Res Hum Retroviruses 2003 Jan 01
PMID:HIV-mediated gammadelta T cell depletion is specific for Vgamma2+ cells expressing the Jgamma1.2 segment. 1258 13


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