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, proliferat e and demonstrate normal Ag-specific memory recall CD4(+) T cell responses. In contrast, CD4(+) T cells from rhesus macaques (RM) experimentally infec ted with SIV lose Ag-specific memory recall responses and develop immunolog ical anergy, To elucidate the mechanisms for these distinct outcomes of len tiviral infection, highly enriched alloreactive CD4(+) T cells from humans, RM, and SM were anergized by TCR-only stimulation (signal 1 alone) and sub sequently challenged with anti-CD3/anti-CD28 Abs (signals 1 + 2), Whereas a lloreactive CD4(+)T cells from humans and RM became anergized, surprisingly , CD4(+) T cells from SM showed marked proliferation and IL-2 synthesis aft er restimulation. This resistance to undergo anergy was not secondary to a global deficiency in anergy induction of CD4(+) T cells from SM since incub ation of CD4(+) T cells with anti-CD3 alone in the presence of rapamycin re adily induced anergy in these cells. The resistance to undergo anergy was r easoned 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 i nvolved in T cell activation showed that the activation of CD4(+) T cells b y 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 contrib ute to the resistance of this species to SIV-induced disease.