Depletion of CD8+ cells in sooty mangabey monkeys naturally infected with simian immunodeficiency virus reveals limited role for immune control of virus replication in a natural host species

SIV infection of sooty mangabeys (SMs), a natural host species, does not cause AIDS despite high-level virus replication. In contrast, SIV infection of nonnatural hosts such as rhesus macaques (RMs) induces an AIDS-like disease. The depletion of CD8(+) T cells during SIV infection of RMs results in marked increases in plasma viremia, suggesting a key role for CD8(+) T cells in controlling levels of SIV replication. To assess the role that CD8(+) T cells play in determining the virologic and immunologic features of nonpathogenic SIV infection in SMs, we transiently depleted CD8(+) T cells in SIV-infected and uninfected SMs using a CD8 alpha-specific Ab (OKT8F) previously used in studies of SIV-infected RMs. Treatment of SMs with the OKT8F Ab resulted in the prompt and profound depletion of CD8(+) T cells. However, in contrast to CD8(+) cell depleted, SIV-infected RMs, only minor changes in the levels of plasma viremia were observed in most SIV-infected SMs during the period of CD8(+) cell deficiency. Those SMs demonstrating greater increases in SIV replication following CD8+ cell depletion also displayed higher levels of CD4(+) T cell activation and/or evidence of CMV reactivation, suggesting that an expanded target cell pool rather than the absence of CD8(+) T cell control may have been primarily responsible for transient increases in viremia. These data indicate that CD8(+) T cells exert a limited influence in determining the levels of SIV replication in SMs and provide additional evidence demonstrating that the absence of AIDS in SIV-infected SMs is not due to the effective control of viral replication by cellular immune responses.