Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0907643 on March 27, 2008

Published online before print March 27, 2008
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(Journal of Leukocyte Biology. 2008;83:1382-1387.)
© 2008 by Society for Leukocyte Biology

S-phase entry leads to cell death in circulating T cells from HIV-infected persons

Scott F. Sieg1, Douglas A. Bazdar and Michael M. Lederman

Case Western Reserve University and University Hospitals of Cleveland, Center for AIDS Research, Cleveland, Ohio, USA

1Correspondence: Case Western Reserve University, School of Medicine, Biomedical Research Building, Room 1020, 2109 Adelbert Rd., Cleveland, OH 44106, USA. E-mail: sfs2{at}case.edu

Central memory T cells are thought to play a critical role in memory T cell homoestasis by undergoing self-renewal and by maturating into effector T cells that mediate immunity at tissue sites. Circulating T cells in S phase of the cell cycle are found at increased frequencies during HIV infection and are predominantly composed of cells with a central memory phenotype. Here, we tested the hypothesis that CD4 and CD8 S-phase T cells have different capacities to complete cell cycle and survive. S-phase T cells in peripheral blood from HIV-infected donors were identified by incubating whole blood with BrdU ex vivo. Upon in vitro cultivation, S-phase T cells were more likely to die than to complete mitotic division. Intrinsic differences were observed between CD4 and CD8 S-phase T cells during incubation. Higher frequencies of CD4+ S-phase T cell underwent apoptosis after incubation in medium alone or after TCR stimulation, and CD4+ S-phase T cells were less readily induced to proliferate after incubation with IL-2 than were CD8+ S-phase T cells. CD4+ and CD8+ S-phase T cells expressed low levels of Bcl-2, which could contribute to their heightened susceptibility to cell death. Intrinsic differences in the proliferation and survival of CD4+ and CD8+ S-phase T cells could influence the homeostatic maintenance of these T cell subsets in HIV disease.

Key Words: T lymphocytes • apoptosis • proliferation






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