Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection

Lisa A. Chakrabarti, Sharon R. Lewin, Linqi Zhang, Agegnehu Gettie, Amara Luckay, Louis N. Martin, Eva Skulsky, David D. Ho, Cecilia Cheng-Mayer, Preston A. Marx

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) remain healthy though they harbor viral loads comparable to those in rhesus macaques that progress to AIDS. To assess the immunologic basis of disease resistance in mangabeys, we compared the effect of SIV infection on T-cell regeneration in both monkey species. Measurement of the proliferation marker Ki-67 by flow cytometry showed that mangabeys harbored proliferating T cells at a level of 3 to 4% in peripheral blood irrespective of their infection status. In contrast, rhesus macaques demonstrated a naturally high fraction of proliferating T cells (7%) that increased two- to threefold following SIV infection. Ki-67+ T cells were predominantly CD45RA-, indicating increased proliferation of memory cells in macaques. Quantitation of an episomal DNA product of T-cell receptor α rearrangement (termed α1 circle) showed that the concentration of recent thymic emigrants in blood decreased with age over a 2-log unit range in both monkey species, consistent with age-related thymic involution. SIV infection caused a limited decrease of el circle numbers in mangabeys as well as in macaques. Dilution of α1 circles by T-cell proliferation likely contributed to this decrease, since α1 circle numbers and Ki-67+ fractions correlated negatively. These findings are compatible with immune exhaustion mediated by abnormal T-cell proliferation, rather than with early thymic failure, in SIV-infected macaques. Normal T-cell turnover in SIV-infected mangabeys provides an explanation for the long-term maintenance of a functional immune system in these hosts.

Original languageEnglish
Pages (from-to)1209-1223
Number of pages15
JournalJournal of Virology
Volume74
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

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