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Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue
Jean-Charles Grivel1, Angelique Biancotto, Yoshinori Ito
1Laboratory of Molecular and Cellular Biophysics, and NASA/NIH Center for Three-Dimensional Tissue Culture, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
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.