Depletion of CD8+ cells in sooty mangabey monkeys naturally infected with simian immunodeficiency virus reveals limited role for immune control of virus replication in a natural host species.
SIV infection of sooty mangabeys (SMs), a natural host species, does not cause AIDS despite high-level virus replication. In contrast, SIV infection of nonnatural hosts such as rhesus macaques (RMs) induces an AIDS-like disease. The depletion of CD8+ T cells during SIV infection of RMs results in marked increases in plasma viremia, suggesting a key role for CD8+ T cells in controlling levels of SIV replication. To assess the role that CD8+ T cells play in determining the virologic and immunologic features of nonpathogenic SIV infection in SMs, we transiently depleted CD8+ T cells in SIV-infected and uninfected SMs using a CD8alpha-specific Ab (OKT8F) previously used in studies of SIV-infected RMs. Treatment of SMs with the OKT8F Ab resulted in the prompt and profound depletion of CD8+ T cells. However, in contrast to CD8+ cell depleted, SIV-infected RMs, only minor changes in the levels of plasma viremia were observed in most SIV-infected SMs during the period of CD8+ cell deficiency. Those SMs demonstrating greater increases in SIV replication following CD8+ cell depletion also displayed higher levels of CD4+ T cell activation and/or evidence of CMV reactivation, suggesting that an expanded target cell pool rather than the absence of CD8+ T cell control may have been primarily responsible for transient increases in viremia. These data indicate that CD8+ T cells exert a limited influence in determining the levels of SIV replication in SMs and provide additional evidence demonstrating that the absence of AIDS in SIV-infected SMs is not due to the effective control of viral replication by cellular immune responses.
Barry
Ashley P
AP
Department of Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Silvestri
Guido
G
Safrit
Jeffrey T
JT
Sumpter
Beth
B
Kozyr
Natalia
N
McClure
Harold M
HM
Staprans
Silvija I
SI
Feinberg
Mark B
MB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001853:Bone Marrow / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D016665:Cercocebus atys / Q000276:immunology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008992:Monkey Diseases / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014779:Virus Replication
D000911:Antibodies, Monoclonal