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Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8+ T cells
Journal article   Open access   Peer reviewed

Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8+ T cells

Constantinos Petrovas, Yvonne M. Mueller, Ioannis D. Dimitriou, Susan R. Altork, Anupam Banerjee, Peter Sklar, Karam C. Mounzer, John D. Altman and Peter D. Katsikis
Blood, v 109(6), pp 2505-2513
15 Mar 2007
PMID: 17095625
url
https://doi.org/10.1182/blood-2006-05-021626View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Immunobiology
What governs the increased apoptosis sensitivity of HIV-specific CD8 + T cells is poorly understood. Here, we examined the involvement of mitochondria in this apoptosis. Remarkably higher mitochondrial mass (MM) was found in HIV-specific compared with CMV-specific CD8 + T cells from HIV + patients and this could not be attributed to their different differentiation status. MM High phenotype characterized those CD8 + T cells from HIV + patients that are sensitive to spontaneous and CD95/Fas-induced apoptosis. CD38 expression did not correlate with high MM, whereas Bcl-2 levels were significantly reduced in both CD38 + and CD38 − HIV-specific CD8 + T cells. Although CD38 + HIV-specific CD8 + T cells were more susceptible to apoptosis, CD38 expression does not explain on its own the selective apoptosis sensitivity of HIV-specific CD8 + T cells, as CD38 − HIV-specific CD8 + T cells were more apoptotic than CD38 + CMV-specific ones. Proapoptotic HIV-specific CD8 + T cells were CD38 + Bcl-2 Low MM High . Copolarization of mitochondria with CD95/Fas capping, very early in CD95/Fas-induced apoptosis of HIV-specific CD8 + T cells, suggests that mitochondria act as an amplification step for this apoptosis. Thus, an extensive mitochondrial network contributes to apoptosis sensitivity of CD8 + T cells and, when this occurs together with reduced levels of Bcl-2 and chronic activation, determines the proapoptotic state of HIV-specific CD8 + T cells.

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Collaboration types
Domestic collaboration
Web of Science research areas
Hematology
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