IL-7 induces proliferation of CD3-/low CD4- CD8- human thymocyte precursors by an IL-2 independent pathway

The proliferation potential of highly purified human CD3-CD4-CD8- (triple negative) and CD3low(lo)CD4-CD8- thymocyte precursors in response to various cytokines was investigated. High in vitro growth ability was observed in response to recombinant human IL-2 (rIL-2) and human rIL-7, both in the absence of any co-mitogen and in combination with phorbol 12-myristate 13-acetate (PMA). Furthermore, the proliferation of these thymocyte precursors in the presence of rIL-7, although accompanied by a significant increase of IL-2 receptor (IL-2R) p55 expression, appeared independent of that mediated by the autocrine IL-2 pathway, since mAbs to IL-2 and IL-2R p55 did not eliminate responsiveness to rIL-7. Synergism of rIL-7 with rIL-2 was also observed, while no cooperation was detectable with rIL-4 or rIL-6. Analysis of surface phenotype and cell cycle status of cells cultured in the presence of rIL-7, both plus and minus PMA, showed that CD3- as well as CD3lo cells readily proliferated to rIL-7. Upregulation of the levels of expression of CD3 antigen was also observed in these cultures. These results, together with the previous characterization of IL-7 as a human pre-B cell and mature T cell growth factor, identify IL-7 as a cytokine with biologic activities on a variety of target cells. They also suggest that IL-7, in analogy with the mouse system, might play a role in human T cell ontogeny.