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

Abstract

The proliferation potential of highly purified human CD3⁻CD4⁻CD8⁻ (triple negative) and CD3^low(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 rlL-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 rlL-7. Synergism of rlL-7 with rlL-2 was also observed, while no cooperation was detectable with rlL-4 or rlL-6. Analysis of surface phenotype and cell cycle status of cells cultured in the presence of rlL-7, both plus and minus PMA, showed that CD3⁻ as well as CD3¹⁰ cells readily proliferated to rlL-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.