title: Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis.
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.
authors.affiliation: Department of Medicine and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Sumpter
authors.forename: Richard
authors.initials: R
authors.lastname: Dunham
authors.forename: Shari
authors.initials: S
authors.lastname: Gordon
authors.forename: Jessica
authors.initials: J
authors.lastname: Engram
authors.forename: Margaret
authors.initials: M
authors.lastname: Hennessy
authors.forename: Audrey
authors.initials: A
authors.lastname: Kinter
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Barbara
authors.initials: B
authors.lastname: Cervasi
authors.forename: Nichole
authors.initials: N
authors.lastname: Klatt
authors.forename: Harold
authors.initials: H
authors.lastname: McClure
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Milush
authors.forename: Silvija
authors.initials: S
authors.lastname: Staprans
authors.forename: Donald L
authors.initials: DL
authors.lastname: Sodora
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D016665:Cercocebus atys; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D018655:Lymphocyte Count; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology