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* Department of Medicine and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Yerkes National Primate Research Center of Emory University, Atlanta, GA 30329; and
¶ Department of Medicine, University of Texas Southwestern, Dallas, TX 75390
In contrast to HIV-infected humans, naturally SIV-infected sooty mangabeys (SMs) very rarely progress to AIDS. Although the mechanisms underlying this disease resistance are unknown, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To define the correlates of preserved CD4+ T cell counts in SMs, we conducted a cross-sectional immunological study of 110 naturally SIV-infected SMs. The nonpathogenic nature of the infection was confirmed by an average CD4+ T cell count of 1,076 ± 589/mm3 despite chronic infection with a highly replicating virus. No correlation was found between CD4+ T cell counts and either age (used as a surrogate marker for length of infection) or viremia. The strongest correlates of preserved CD4+ T cell counts were a low percentage of circulating effector T cells (CD28–CD95+ and/or IL-7R/CD127–) and a high percentage of CD4+CD25+ T cells. These findings support the hypothesis that the level of immune activation is a key determinant of CD4+ T cell counts in SIV-infected SMs. Interestingly, we identified 14 animals with CD4+ T cell counts of <500/mm3, of which two show severe and persistent CD4+ T cell depletion (<50/mm3). Thus, significant CD4+ T cell depletion does occasionally follow SIV infection of SMs even in the context of generally low levels of immune activation, lending support to the hypothesis of multifactorial control of CD4+ T cell homeostasis in this model of infection. The absence of AIDS in these "CD4low" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4+ T cell depletion.
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1 Address correspondence and reprint requests to Dr. Guido Silvestri, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 705 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104. E-mail address: gsilvest{at}mail.med.upenn.edu
2 Abbreviations used in this paper: SM, sooty mangabey; BAL, bronchioalveolar lavage; IEL, intraepithelial lymphocyte; LN, lymph node; LPL, lamina propria lymphocyte; RB, rectal biopsy; SIVmac, SIV infecting rhesus macaques; SIVsmm, SIV infecting SMs; TE, naïve T cell; TM, memory T cell; TN, naive T cell; Treg, regulatory T.
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