Frequencies of FoxP3+ naive T cells are related to both viral load and naive T cell proliferation responses in HIV disease

HIV infection results in depletion and dysfunction of naive CD4(+) T cells. The mechanisms underlying these deficiencies are not understood. We investigated the frequencies of CD4(+) naive subsets in HIV disease as defined by expression of CD25 and/or FoxP3 and the relationship of these frequencies to naive T cell proliferation function. We observed increased proportions of CD25(+)FoxP3(+) and CD25(+)FoxP3(-) cells and decreased proportions of CD25(-)FoxP3(-) cells within the naive CD4(+) cell compartment from HIV-infected persons compared with findings in healthy donors. These perturbations were related to higher plasma HIV RNA levels but not with higher immune activation, as measured by the proportions of CD38(+) memory CD4(+) T cells. Naive T cell proliferation responses to mitogen stimulation were inversely related to the frequencies and absolute numbers of FoxP3(+) naive T cells. MDA, a marker of oxidative stress, and sCD14, a marker of monocyte activation and a surrogate for microbial translocation, were increased in serum samples from HIV+ donors; however, neither marker was related to naive T cell function in HIV+ donors. These observations suggest that alterations in naive T cell subset frequencies could contribute to naive T cell dysfunction in HIV disease, but these alterations are not necessarily the result of chronic immune activation. J. Leukoc. Biol. 90: 621-628; 2011.