Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection

Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4(+) T cell count and a strong HIV-specific CD4(+) T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a crosssectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4(+) T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57(-)), and more frequently produced IFN-gamma or IL-2 than CD4(+) T cells from HIV-1-infected donors. Polyfunctional (1FN-gamma(+)/1L-2(+)) HIV-specific CD4(+) T cells were found exclusively in HIV-2(+) donors. The disparity in CD4(+) T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8(+) T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4(+) T cell response that is associated with delayed disease progression in the majority of infected people.