Background:  We have previously shown that naturally SIV-infected sooty mangabeys (SM) mount a substantial cellular immune response to SIV. To determine its effect on maintenance of plasma SIV, we investigated the relationship between SIV viral load and the frequency of SIV-specific T lymphocytes in a cohort of naturally infected SM.

Methods:  Peripheral blood mononuclear cells from 25 naturally SIV-infected SM were sampled at 3 or more time points (total 90 time points) during a 3-to-15-month period. Plasma SIV RNA and IFN-g ELISpot response to peptide pools spanning all 9 SIVmac239 proteins were measured at all time points. The frequency of SIV-specific CD4⁺ and CD8⁺ T lymphocytes was determined by intracellular cytokine staining (ICS) assay in 13/25 animals. Correlation between viral load and magnitude of cellular immunity was measured by the Spearman Rank Correlation test, while the Mann-Whitney U test was used to compare differences between animals with low- or high-level viremia.

Results:  The plasma viral load ranged between 4.3´10² and 1.7´10⁶ SIV RNA copies/mL (median 1.1´10⁵ copies/mL) and in the majority of animals varied less than 7-fold with time. The magnitude of interferon-g (INF-g) ELISpot response to any 1 or all 9 SIVmac239 proteins did not correlate significantly with the level of plasma SIV viremia. Similarly, the breadth of the SIV-specific response also did not correlate with plasma SIV viral load. Since ELISpot assays were performed on unfractionated peripheral blood mononuclear cells (PBMC), this analysis did not differentiate between CD4^+- and CD8^+- mediated T lymphocyte responses. By intracellular cytokine staining (ICS) assay, Gag-specific CD8⁺ T lymphocytes ranging between 0.11% and 1.7% (median 0.21%) were detected in 9/13 SM, while Env-specific CD8⁺ T lymphocytes ranging from 0.05% to 1.56% (median 0.37%) were detected in 10/13 SM. Although an inverse correlation between viral load and the frequency of Gag-specific (Rho – 0.59) or Env-specific (Rho – 0.50) CD8⁺ T lymphocytes did not reach statistical significance, the frequency of circulating Gag and Env-specific CD8⁺ T lymphocytes in SM with SIV viremia <10⁵ SIV RNA copies/mL was significantly higher (both p = 0.03, Mann-Whitney U test) than that observed in SM with SIV viremia >10⁵ SIV RNA copies/mL.

Conclusion:  These data suggest a role for SIV-specific CD8⁺ T lymphocytes in limiting viral replication during the course of natural SIV infection in SM.

Keywords: SIV pathogenesis; sooty mangabeys; cellular immunity