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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2505-2513. Prepublished online as a Blood First Edition Paper on November 9, 2006; DOI 10.1182/blood-2006-05-021626. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-05-021626v1 109/6/2505    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Petrovas, C. Articles by Katsikis, P. D. Search for Related Content PubMed PubMed Citation Articles by Petrovas, C. Articles by Katsikis, P. D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8+ T cells Constantinos Petrovas1, Yvonne M. Mueller1, Ioannis D. Dimitriou1, Susan R. Altork1, Anupam Banerjee1, Peter Sklar2, Karam C. Mounzer3, John D. Altman4, and Peter D. Katsikis1 1 Department of Microbiology and Immunology and Institute for Molecular Medicine and Infectious Disease and 2 Department of Medicine, Drexel University College of Medicine, Drexel University, Philadelphia, PA; 3 Philadelphia FIGHT, Philadelphia, PA; 4 Department of Microbiology and Immunology, Emory University, Atlanta, GA 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. MMHigh 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-2LowMMHigh. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Genesca, T. Rourke, J. Li, K. Bost, B. Chohan, M. B. McChesney, and C. J. Miller Live Attenuated Lentivirus Infection Elicits Polyfunctional Simian Immunodeficiency Virus Gag-Specific CD8+ T Cells with Reduced Apoptotic Susceptibility in Rhesus Macaques that Control Virus Replication after Challenge with Pathogenic SIVmac239 J. Immunol., October 1, 2007; 179(7): 4732 - 4740. [Abstract] [Full Text] [PDF]

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