Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis.
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.
Sumpter
Beth
B
Department of Medicine and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Dunham
Richard
R
Gordon
Shari
S
Engram
Jessica
J
Hennessy
Margaret
M
Kinter
Audrey
A
Paiardini
Mirko
M
Cervasi
Barbara
B
Klatt
Nichole
N
McClure
Harold
H
Milush
Jeffrey M
JM
Staprans
Silvija
S
Sodora
Donald L
DL
Silvestri
Guido
G
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