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 Klatt, Harold McClure, Jeffrey M. Milush, Silvija Staprans, Donald L. Sodora, Guido Silvestri

Research output: Contribution to journalArticle

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/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 CB4+ T cell counts were a low percentage of circulating effector T cells (CD28-CD95+ and/or IL-7R/CB127-) and a high percentage of CD4+CB25+ 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/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.

Original languageEnglish (US)
Pages (from-to)1680-1691
Number of pages12
JournalJournal of Immunology
Volume178
Issue number3
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sumpter, B., Dunham, R., Gordon, S., Engram, J., Hennessy, M., Kinter, A., Paiardini, M., Cervasi, B., Klatt, N., McClure, H., Milush, J. M., Staprans, S., Sodora, D. L., & Silvestri, G. (2007). Correlates of preserved CD4+ T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: Implications for AIDS pathogenesis. Journal of Immunology, 178(3), 1680-1691. https://doi.org/10.4049/jimmunol.178.3.1680