Interleukin-7 promotes the generation of phenotypically mature CD45RA positive human thymocytes in vitro

Abstract

IL-7 has been shown to support the proliferation of several cell types including human and murine thymocytes. We have investigated the influence of IL-7 on human thymocyte growth and maturation. In a serum-free culture system, recombinant human interleukin-7 (IL-7) (200 U/ml) stimulated nylon wool purified human thymocytes to express a mature phenotype. IL-7 promoted the generation of a population of large thymocytes which expressed high density CD3, CD4 and/or CD8, and high density CD45RA after 10 to 14 days in culture. The induction of CD45RA was not a transient event, since large CD45RA + cells remained “bright” CD45RA + up to 12 days after IL-7 was removed from cultures. IL-7 did support thymocyte proliferation. However, the IL-7-induced generation of large CD45RA + thymocytes was not due to proliferation of a small subset because large CD45RA + thymocytes also appeared in the presence of proliferation inhibitors. In order to identify IL-7-responsive thymocyte subsets, highly purified CD45RA − subsets at distinct stages of maturation were tested. CD3 −, “dim” CD3 + and “bright” CD3 + subsets each responded to IL-7 with de novo expression of CD45RA. These data provide evidence that IL-7 supports phenotypic changes in both mature and immature subsets of human thymocytes, and indicate that IL-7 may play an important role in T cell development in the thymus.