IMMUNOBIOLOGY IL-7 sustains CD31 expression in human naive CD4 T cells and preferentially expands the CD31 subset in a PI3K-dependent manner

The CD31 subset of human naive CD4 T cells is thought to contain the popula-tion of cells that have recently emigrated from the thymus, while their CD31 coun-terparts have been proposed to originate from CD31 cells after homeostatic cell division. Naive T-cell maintenance is known to involve homeostatic cytokines such as interleukin-7 (IL-7). It remains to be investigated what role this cytokine has in the homeostasis of naive CD4 T-cell subsets defined by CD31 expres-sion. We provide evidence that IL-7 exerts a preferential proliferative effect on CD31 naive CD4 T cells from adult peripheral blood compared with the CD31 subset. IL-7–driven proliferation did not result in loss of CD31 expression, suggesting that CD31 naive CD4 T cells can undergo cytokine-driven homeostatic prolifera-tion while preserving CD31. Furthermore, IL-7 sustained or increased CD31 expres-sion even in nonproliferating cells. Both proliferation and CD31 maintenance were dependent on the activation of phospho-inositide 3-kinase (PI3K) signaling. Taken together, our data suggest that during adulthood CD31 naive CD4 T cells are maintained by IL-7 and that IL-7–based therapies may exert a preferential effect on this population. (Blood. 2009;113: 2999-3007