In vivo expansion of CD4+CD45RO-CD25+ T cells expressing foxP3 in IL-2-treated HIV-infected patients

Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4(+)CD45RO(-)CD25(+) cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4(+)CD45RO-CD25(+) cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45RO(-)CD25(-) or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25(+) cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45RO(+)CD25(+)high cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4(+)CD45RO(-)CD25(+) cells that express high levels of foxP3 but exert weak suppressive function. These CD4(+)CD25(+) cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4(+) T cell pool.