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Summary The capacity of the immune system to respond efficiently to new antigens depends upon a continuous source of naive CD4+ T cells. Such cells exit from the thymus and join the recirculated T‐cell pool. Factors present at the sites of naive CD4+ T‐cell circulation must be responsible for their survival, since upon removal from their host, naive CD4+ T cells die. However, such factors remain unknown. The presence of the cytokine interleukin‐7 (IL‐7) in secondary lymphoid organs and the continuous expression of its receptor on naive CD4+ T cells prompted us to examine the possibility that IL‐7 might be a survival factor for naive CD4+ T cells. Using naive CD4+ T cells isolated from cord blood we show that IL‐7, but not IL‐2, can maintain naive CD4+ T‐cell viability in vitro for at least 15 days. In addition, we find that IL‐7 can induce modest proliferation of naive CD4+ T cells without affecting either their cell surface phenotype or their ability to respond to antigenic stimulation. We also find that after anti‐CD3 stimulation, naive CD4+ T cells lose that ability to respond to IL‐7. However, if cells are primed with IL‐7 prior to antigenic stimulation, their proliferative responses are enhanced. Together, these data suggest a novel and important role for IL‐7 in the maintenance and maturation of naive CD4+ T cells, ensuring that they can respond maximally when they first meet antigen in secondary lymphoid tissue. [ABSTRACT FROM AUTHOR]