IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire

We have investigated the regulation of adult and cord blood CD45RA(+) T cell proliferation and apoptosis to identify factors that may control the naive T cell pool. Cord CD45RA(+) T cells were highly susceptible to spontaneous apoptosis as compared with CD45RA(+) T cells from adults. Apoptosis was prevented by the addition of IL-2, IL-4, IL-7, and IL-15 which signal via the gamma-chain of the IL-2 receptor. IL-7 prevented the decrease in Bcl-2 and Bcl-x(L) and induced cell cycling in up to 20% of cord T cells after 8 days, resulting in a threefold increase in cord T cell numbers. However, the expanded cells retained a CD45RA(+)CD45RO(-) phenotype. Similar results were obtained with adult CD45RA(+) T cells. IL-7-expanded CD45RA(+)RO(-) T cells expressed CD45RO after stimulation through the TCR, Investigations into the regulation of replicative senescence showed that after 12 days in culture with IL-7, cord blood CD45RA(+) T cell proliferation resulted in telomere shortening. Nevertheless, IL-7-expanded cord blood T cells still maintained longer telomeres than unstimulated adult T cells. IL-7 but not IL-2 could directly induce high telomerase activity which probably retarded the rate of telomere shortening in cord blood T cells. These results suggest that proliferation induced by IL-7 may be important for extrathymic expansion of neonatal CD45RA(+) T cells and may also contribute to the maintenance of the adult CD45RA(+) T cell pool.