Relative resistance in the development of T cell anergy in CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys.
Despite high viral loads, T cells from sooty mangabey (SM) monkeys that are naturally infected with SIV but remain clinically asymptomatic, proliferate and demonstrate normal Ag-specific memory recall CD4(+) T cell responses. In contrast, CD4(+) T cells from rhesus macaques (RM) experimentally infected with SIV lose Ag-specific memory recall responses and develop immunological anergy. To elucidate the mechanisms for these distinct outcomes of lentiviral infection, highly enriched alloreactive CD4(+) T cells from humans, RM, and SM were anergized by TCR-only stimulation (signal 1 alone) and subsequently challenged with anti-CD3/anti-CD28 Abs (signals 1 + 2). Whereas alloreactive CD4(+)T cells from humans and RM became anergized, surprisingly, CD4(+) T cells from SM showed marked proliferation and IL-2 synthesis after restimulation. This resistance to undergo anergy was not secondary to a global deficiency in anergy induction of CD4(+) T cells from SM since incubation of CD4(+) T cells with anti-CD3 alone in the presence of rapamycin readily induced anergy in these cells. The resistance to undergo anergy was reasoned to be due to the ability of CD4(+) T cells from SM to synthesize IL-2 when incubated with anti-CD3 alone. Analysis of phosphorylated kinases involved in T cell activation showed that the activation of CD4(+) T cells by signal 1 in SM elicited a pattern of response that required both signals 1 + 2 in humans and RM. This function of CD4(+) T cells from SM may contribute to the resistance of this species to SIV-induced disease.
Bostik
P
P
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. pbostik@emory.edu
Mayne
A E
AE
Villinger
F
F
Greenberg
K P
KP
Powell
J D
JD
Ansari
A A
AA
D000328:Adult; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016665:Cercocebus atys / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007113:Immunity, Innate; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000276:immunology; D008253:Macaca mulatta; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D020123:Sirolimus / Q000494:pharmacology
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D016853:Muromonab-CD3; D016572:Cyclosporine; D020928:Mitogen-Activated Protein Kinases; D020123:Sirolimus; D006918:Hydroxyurea