Correlates of preserved CD4+ T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS …

B Sumpter, R Dunham, S Gordon, J Engram… - The Journal of …, 2007 - journals.aai.org
B Sumpter, R Dunham, S Gordon, J Engram, M Hennessy, A Kinter, M Paiardini, B Cervasi…
The Journal of immunology, 2007journals.aai.org
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 …
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.
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