Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.

Meyaard, Linde; Otto, S. A.; Keet, I. P. M.; Roos, M. T. L.; Miedema, Frank

doi:10.1172/jci117105

Cited by 142 publications

(84 citation statements)

References 35 publications

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“…Termination of the long latency of AIDS in patients infected with HIV-1 is marked by a profound depletion of CD4 + T cells and the decline of HIV-1 speci®c cytotoxic CD8 + T cells (Meyaard et al, 1992(Meyaard et al, ,1994. The mechanisms by which HIV-1 kills immune cells are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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The e ects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stabletransfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This e ect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by di erent stimuli. Using a cyto¯uorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Dc m ) followed by an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-X L and Bax proteins was not a ected by the presence of Tat. Regardless of the steady state of the Bax protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm. The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the speci®c inhibitor, z-DEVD-cmk, did not a ect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, we found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Dc m disruption detected in these cells. In addition, HIV-1 Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.

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Section: Introductionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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“…Ameisen and Capron [3] were the first to propose that in HIV infection interaction of soluble gp 120 with CD4, previously shown to lead to impaired lymphocyte function [26], could prime CD4 + T cells for PCD, which might provide a mechanism for CD4 + T cell loss. Indeed, peripheral blood mononuclear cells (PBMC) from HIV-infected individuals die due to PCD in vitro [59,61,78,94,95,117,121]. PCD can be enhanced by activation in vitro with T cell receptor (TCR)/CD3 monoclonal antibodies (mAb), lectins, superantigens or ionomycin [59,61,94,117].…”

Section: Programmed Death Of T Cells In Hiv Infectionmentioning

confidence: 99%

“…PCD can be enhanced by activation in vitro with T cell receptor (TCR)/CD3 monoclonal antibodies (mAb), lectins, superantigens or ionomycin [59,61,94,117]. PCD occurs in both CD4 + and CD8 + T cells and phenotypical analysis suggests that higher percentages of CD8 + cells are dying [23,59,94,95].…”

Section: Programmed Death Of T Cells In Hiv Infectionmentioning

confidence: 99%

“…Because they form the largest fraction of T cells, numerically the majority of cells dying during primary infection are activated, CD8+CD45RO + cells. However, all CD8 + T cell subsets contain cells dying due to PCD and there is no evidence for preferential death in one specific subset of cells [78,95]. In the asymptomatic phase of HIV infection there is a variable but, compared to HIV-negative controls, consistently increased percentage of cells dying due to PCD [59,94,95].…”

Section: Programmed Death Of T Cells In Hiv Infectionmentioning

confidence: 99%

“…However, all CD8 + T cell subsets contain cells dying due to PCD and there is no evidence for preferential death in one specific subset of cells [78,95]. In the asymptomatic phase of HIV infection there is a variable but, compared to HIV-negative controls, consistently increased percentage of cells dying due to PCD [59,94,95]. We and others have shown that PCD does not correlate with CD4 + T cell numbers in asymptomatic individuals, nor with viral load, arguing against dramatic changes in the extent of PCD with progression to disease [82,95,107].…”

Section: Programmed Death Of T Cells In Hiv Infectionmentioning

confidence: 99%

See 2 more Smart Citations

Immune dysregulation and CD4+ T cell loss in HIV-1 infection

Meyaard

Miedema

1997

Springer Semin Immunopathol

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Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

et al. 1997

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Peripheral blood mononuclear cells from many asymptomatic HIV‐infected patients exhibit defects in cytokine production and impaired proliferative responses in vitro but the mechanisms underlying this subclinical immune deficiency are controversial. To determine whether abnormalities in the earliest events following receptor engagement may help to explain the in vitro immune dysfunction, we measured the inducibility of the early activation marker CD69 in T cells from asymptomatic HIV‐infected individuals in response to stimulation with anti‐CD2 or anti‐CD3 mAb. In a whole blood assay, we found that induction of CD69 was markedly impaired in CD4+ T cells from later‐stage HIV‐infected patients (CD4 counts 200–400/mm3) compared to uninfected controls. Among early stage patients (CD4 > 400/mm3), a subset (29%) had impaired CD69 induction. CD69 responses were equally depressed after stimulation through the CD3 or CD2 receptor pathways. Survey of a panel of immunophenotypic markers and propensity for apoptosis demonstrated a significant association between depressed induction of CD69 and decreased percentages of CD4+CD26+ and CD4+CD95+ cells but no association with the level of apoptosis. These data indicate that defects in T lymphocyte activation through CD3 and CD2 can be measured within hours of receptor stimulation in asymptomatic HIV‐infected individuals and might be useful to monitor as an indicator of immune function in these patients. Cytometry 30:1–9, 1997. © 1997 Wiley‐Liss, Inc.

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Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.

Cited by 142 publications

References 35 publications

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Immune dysregulation and CD4+ T cell loss in HIV-1 infection

Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

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