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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 Species¹

Ashley P. Barry^*, Guido Silvestri^2,*,, Jeffrey T. Safrit^*, Beth Sumpter^*, Natalia Kozyr^*, Harold M. McClure, Silvija I. Staprans^3,*,, and Mark B. Feinberg^4,*,,

^* Emory Vaccine Center, Department of Medicine, and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Yerkes National Primate Research Center of Emory University, Atlanta, GA 30329

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-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 AI49155, P51 RR000165, and P30 AI50409.

² Current address: Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

³ Current address: Merck Vaccine Division, Merck and Company, West Point, PA 19486.

⁴ Address correspondence and reprint requests to Dr. Mark B. Feinberg at the current address: Merck Vaccine Division, Merck and Company, 770 Sumneytown Pike, P.O. Box 4, West Point, PA 19486. E-mail address: mark_feinberg{at}merck.com

⁵ Abbreviations used in this paper: RM, rhesus macaque; SM, sooty mangabey.