In vivo analysis of Fas/FasL interactions in HIV-infected patients

Andrew D. Badley, David H. Dockrell, Alicia Algeciras, Steve Ziesmer, Alan Landay, Michael M. Lederman, Elizabeth Connick, Harold Kessler, Daniel Kuritzkes, David H. Lynch, Patrick Roche, Hideo Yagita, Carlos V. Paya

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130 Scopus citations

Abstract

Recent insights into the pharmacological control of HIV replication and the molecular mechanisms of peripheral T cells homeostasis allowed us to investigate in vivo the mechanisms mediating T cell depletion in HIV-infected patients. Before the initiation of highly active antiretroviral therapy (HAART), a high degree of lymphoid tissue apoptosis is present, which is reduced upon HAART initiation (P < 0.001) and directly correlates with reduction of viral load and increases of peripheral T lymphocytes (P < 0.01). Because Fas/FasL interactions play a key role in peripheral T lymphocyte homeostasis, we investigated the susceptibility to Fas-mediated apoptosis in peripheral T lymphocytes and of FasL expression in lymphoid tissue before and during HAART. High levels of Fas-susceptibility found in peripheral CD4 T lymphocytes before HAART were significantly reduced after HAART, coinciding with decreases in viral load (P = 0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0.01). However, the increased FasL expression in the lymphoid tissue of HIV-infected individuals was not reduced after HAART. These results demonstrate that lymphoid tissue apoptosis directly correlates with viral load and peripheral T lymphocyte numbers, and suggest that HIV- induced susceptibility to Fas-dependent apoptosis may play a key role in the regulation of T cell homeostasis in HIV-infected individuals.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number1
DOIs
StatePublished - Jul 1 1998

Keywords

  • Apoptosis
  • CD4 T cells
  • FasL
  • HIV
  • Highly active retroviral therapy

ASJC Scopus subject areas

  • Medicine(all)

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    Badley, A. D., Dockrell, D. H., Algeciras, A., Ziesmer, S., Landay, A., Lederman, M. M., Connick, E., Kessler, H., Kuritzkes, D., Lynch, D. H., Roche, P., Yagita, H., & Paya, C. V. (1998). In vivo analysis of Fas/FasL interactions in HIV-infected patients. Journal of Clinical Investigation, 102(1), 79-87. https://doi.org/10.1172/JCI2691