Correlates of Preserved CD4(+) T Cell Homeostasis During Natural, Nonpathogenic Simian Immunodeficiency Virus Infection of Sooty Mangabeys: Implications for AIDS Pathogenesis

Beth Sumpter, Richard Dunham, Shari Gordon, Jessica Engram, Margaret Hennessy, Audrey Kinter, Mirko Paiardini, Barbara Cervasi, Nichole R Klatt, Harold McClure, Jeffrey Milush, Silvija Staprans, Donald Sodora, Guido Silvestri

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

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/mm(3) 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/mm(3), of which two show severe and persistent CD4(+) T cell depletion (<50/mm(3)). 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 "CD4(low)" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4(+) T cell depletion.
Original languageEnglish (US)
Pages (from-to)1680
Number of pages1691
JournalJournal of Immunology
Volume178
StatePublished - Feb 1 2007

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