Bystander CD4 + T Lymphocytes Survive in HIV-Infected Human Lymphoid Tissue

Abstract

HIV infection is associated with depletion of CD4⁺ T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected("bystander") CD4⁺ T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4⁺ T cells that had not yet been infected. These CD4⁺ T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4⁺ T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4⁺ T cells.