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

Abstract

ABSTRACT 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.