Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys.
HIV-infected humans and SIV-infected rhesus macaques experience a rapid and dramatic loss of mucosal CD4+ T cells that is considered to be a key determinant of AIDS pathogenesis. In this study, we show that nonpathogenic SIV infection of sooty mangabeys (SMs), a natural host species for SIV, is also associated with an early, severe, and persistent depletion of memory CD4+ T cells from the intestinal and respiratory mucosa. Importantly, the kinetics of the loss of mucosal CD4+ T cells in SMs is similar to that of SIVmac239-infected rhesus macaques. Although the nonpathogenic SIV infection of SMs induces the same pattern of mucosal target cell depletion observed during pathogenic HIV/SIV infections, the depletion in SMs occurs in the context of limited local and systemic immune activation and can be reverted if virus replication is suppressed by antiretroviral treatment. These results indicate that a profound depletion of mucosal CD4+ T cells is not sufficient per se to induce loss of mucosal immunity and disease progression during a primate lentiviral infection. We propose that, in the disease-resistant SIV-infected SMs, evolutionary adaptation to both preserve immune function with fewer mucosal CD4+ T cells and attenuate the immune activation that follows acute viral infection protect these animals from progressing to AIDS.
Gordon
Shari N
SN
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Klatt
Nichole R
NR
Bosinger
Steven E
SE
Brenchley
Jason M
JM
Milush
Jeffrey M
JM
Engram
Jessica C
JC
Dunham
Richard M
RM
Paiardini
Mirko
M
Klucking
Sara
S
Danesh
Ali
A
Strobert
Elizabeth A
EA
Apetrei
Cristian
C
Pandrea
Ivona V
IV
Kelvin
David
D
Douek
Daniel C
DC
Staprans
Silvija I
SI
Sodora
Donald L
DL
Silvestri
Guido
G
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016665:Cercocebus atys / Q000276:immunology* / Q000821:virology; D007108:Immune Tolerance; D007156:Immunologic Memory; D020545:Respiratory Mucosa / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus
D000998:Antiviral Agents
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