Vaccination with SIVmac239Δnef activates CD4+ T cells in the absence of CD4+ T‐cell loss

Abstract

Pathogenic HIV and SIV infections characteristically deplete central memory CD4(+) T cells and induce chronic immune activation, but it is controversial whether this also occurs after vaccination with attenuated SIVs and whether depletion or activation of CD4(+) T-cell play roles in protection against wild-type virus challenge. Rhesus macaques were vaccinated with SIVmac239Deltanef and quantitative and phenotypic polychromatic flow cytometry analyses were performed on mononuclear cells from blood, lymph nodes and rectal biopsies. Animals vaccinated with SIVmac239Deltanef demonstrated no loss of CD4(+) T cells in any tissue, and in fact CCR5(+) and CD28(+)CD95(+) central memory CD4(+) T cells were significantly increased. In contrast, CD4(+) T-cell numbers and CCR5 expression significantly declined in unvaccinated controls challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as 3-fold over baseline in all tissues after SIVmac239Deltanef vaccination then declined following primary infection. We demonstrated in this study that SIVmac239Deltanef vaccination did not deplete CD4(+) T cells but transiently activated and expanded the memory cell population. However, increases in numbers and activation of memory CD4(+) T cells did not appear to influence protective immunity.