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

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) remain healthy though they harbor viral loads comparable to those in rhesu s macaques that progress to AIDS. To assess the immunologic basis of diseas e resistance in mangabeys, we compared the effect of SIV infection on T-cel l regeneration in both monkey species. Measurement of the proliferation mar ker 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 infec tion status. In contrast, rhesus macaques demonstrated a naturally high fra ction of proliferating T cells (7%) that increased two- to threefold follow ing SIV infection. Ki-67(+) T cells were predominantly CD45RA(-), indicatin g increased proliferation of memory cells in macaques. Quantitation of an e pisomal DNA product of T cell receptor cu rearrangement (termed alpha 1 cir cle) showed that the concentration of recent thymic emigrants in blood decr eased with age over a 2-log unit range in both monkey species, consistent w ith age-related thymic involution. SIV infection caused a limited decrease of alpha 1 circle numbers in mangabeys as well as in macaques. Dilution of alpha 1 circles by T-cell proliferation likely contributed to this decrease , since al circle numbers and Ki-67(+) fractions correlated negatively. The se findings are compatible with immune exhaustion mediated by abnormal T-ce ll proliferation, rather than with early thymic failure, in SIV-infected ma caques. Normal T-cell turnover in SIV-infected mangabeys provides an explan ation for the long-term maintenance of a functional immune system in these hosts.