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Journal of Virology, September 2000, p. 8077-8084, Vol. 74, No. 17
0022-538X/00/$04.00+0

Human Immunodeficiency Virus Type 1 Induces Apoptosis in CD4+ but Not in CD8+ T Cells in Ex Vivo-Infected Human Lymphoid Tissue

Jean-Charles Grivel, Nina Malkevitch, and Leonid Margolis*

Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Received 21 September 2000/Accepted 8 June 2000

Progression of human immunodeficiency virus (HIV) disease is associated with massive death of CD4+ T cells along with death and/or dysfunction of CD8+ T cells. In vivo, both HIV infection per se and host factors may contribute to the death and/or dysfunction of CD4+ and CD8+ T cells. Progression of HIV disease is often characterized by a switch from R5 to X4 HIV type 1 (HIV-1) variants. In human lymphoid tissues ex vivo, it was shown that HIV infection is sufficient for CD4+ T-cell depletion. Here we address the question of whether infection of human lymphoid tissue ex vivo with prototypic R5 or X4 HIV variants also depletes or impairs CD8+ T cells. We report that whereas productive infection of lymphoid tissue ex vivo with R5 and X4 HIV-1 isolates induced apoptosis in CD4+ T cells, neither viral isolate induced apoptosis in CD8+ T cells. Moreover, in both infected and control tissues we found similar numbers of CD8+ T cells and similar production of cytokines by these cells in response to phorbol myristate acetate or anti-CD3-anti-CD28 stimulation. Thus, whereas HIV-1 infection per se in human lymphoid tissue is sufficient to trigger apoptosis in CD4+ T cells, the death of CD8+ T cells apparently requires additional factors.

* Corresponding author. Mailing address: NIH, Bldg. 10, Rm. 10D14, Bethesda, MD 20892. Phone: (301) 594-2476. Fax: (301) 480-0857. E-mail: margolis{at}helix.nih.gov.

Journal of Virology, September 2000, p. 8077-8084, Vol. 74, No. 17
0022-538X/00/$04.00+0


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