Background: Naturally SIV-infected sooty mangabeys (SMs) do not develop AIDS and maintain near normal CD4+ T cell count despite many years of high-level virus replication. It has been hypothesized that SIV-specific CD8+ T cell-mediated responses may be instrumental in determining the absence of clinically relevant immunodeficiency in these animals. To test this hypothesis we have measured the magnitude and breadth of SIV-specific CD8+ T cell-mediated responses in a large group of naturally SIV-infected SMs.

Methods: SIV-specific CD8+ T cell responses to pools of overlapping peptides spanning the four major antigenic proteins of SIVmac239 (gag, pol, env, nef) were measured using intracellular cytokine staining for IFN-g production in 74 naturally SIV-infected SMs hosted at the Yerkes Primate Center. A positive response was defined as at least 0.01% of specific peptide-induced IFN-g production by CD8+ T cells (i.e., 0.01% higher than the DMSO only control). SIV plasma viremia was measured by RT-PCR. CD4+ T cell count was determined by flow cytometry.

Results: (i) Positive CD3+CD8+ T cell responses were detected in 48 out of 74 (64.8%) naturally SIV-infected SMs; (ii) the hierarchy of immunogenicity was env (47.3% responses), gag (40.5%), pol (27.0%), and nef (13.5%); (iii) the magnitude of the responses was generally low, with only 6 out of 74 (8.3%) animals showing >1% of total SIV-specific CD8+ T cell responses, and 58/74 (78.4%) animals showing a total SIV-specific CD8+ T cell response either absent or <0.2%; (iv) no correlation was found between either breadth or magnitude of SIV-specific CD8+ T cell responses and either viral load or CD4+ T cell count. In addition, no significant differences in viral load or CD4+ T cell count were observed between "responders" and "non-responders".

Conclusions: SIV-specific CD8+ T cell-mediated responses are limited (i.e. <0.2% of total CD8+ T cells) in the majority of naturally SIV-infected SMs. When present, their breadth and magnitude do not correlate with either control of viral replication or maintenance of normal CD4+ T cell count. These data indicate that, in SIV-infected SMs, CD8+ T cell mediated cellular immune responses do not play a major role in determining the immunological and clinical course of the infection.

Keywords: SIV-Infection of Natural Hosts; CD8 T Cell Responses; T Cell Function