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Presence of Suppressor HIV-Specific CD8⁺ T Cells Is Associated with Increased PD-1 Expression on Effector CD8⁺ T Cells¹

Mohamed Elrefaei^2,*, Chris A. R. Baker^*, Norman G. Jones^*, David R. Bangsberg and Huyen Cao^*

^* California Department of Public Health, Richmond, CA 94804; and Department of Medicine, University of California, San Francisco, CA 94143

Mechanisms leading to the observed immune dysregulation in HIV-1 infection are not well understood. HIV-specific IL-10-positive CD8⁺ T cells are increased in advanced HIV disease. We have previously reported that Gag-specific IL-10-positive CD8⁺ T cells suppressed cytolysis. In this study we describe the suppressive effect of Nef-specific IL-10-positive CD8⁺ T cells. Interestingly, simultaneous removal of both Gag- and Nef-specific IL-10-positive CD8⁺ T cells led to higher HIV-specific cytolysis compared with the removal of Nef-specific IL-10-positive CD8⁺ T cells alone. We also examined the level of programmed cell death-1 (PD-1) as a measure of immune dysfunction in association with IL-10-positive suppressor CD8⁺ T cells. The level of PD-1 expression on CD107-positive effector CD8⁺ T cells was significantly increased when IL-10-positive suppressor CD8⁺ T cells were present (p < 0.05). Our results suggest that IL-10-positive suppressor CD8⁺ T cells contribute to the immune dysfunction observed in advanced HIV infection and that the concomitant presence of multiple IL-10-positive CD8⁺ T cell populations may have an additive suppressive effect.

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 AI43885, MH54907, and AI71772.

² Address correspondence and reprint requests to Dr. Mohamed Elrefaei, California Department of Public Health, 850 Marina Bay Parkway, VRDL, Richmond, CA 94804. E-mail address: melrefae{at}cdph.ca.gov

³ Abbreviations used in this paper: PD-1, programmed cell death-1; ILT, Ig-like transcript; PDL-1, PD-1 ligand.

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