INVOLVEMENT OF THE INTERLEUKIN-4 PATHWAY IN THE GENERATION OF FUNCTIONAL GAMMA-DELTA-T-CELLS FROM HUMAN PRO-T CELLS

We have used the technique of in situ hybridization to investigate the transcription of genes encoding the CD3 complex and the lymphokine interleukin 4 (IL-4) by human pro-T cells-i.e., cells that phenotypically resemble those T-cell precursors that colonize the thymus during early intrathymic development. CD1-2-3-4-7+8-45+ pro-T cells isolated from postnatal thymi via immunoselection with a panel of specific monoclonal antibodies are already committed to the T-cell lineage because most of them transcribe the genes encoding the delta and epsilon-chains of the CD3 complex. About half of such pro-T cells synthesize IL-4 mRNA in the absence of any exogenous stimulation. Upon culture with IL-4, pro-T cells extensively proliferate and differentiate into functionally competent, mature gamma-delta T cells expressing a T-cell receptor repertoire similar to that of gamma-delta T cells that can be found in postnatal thymus. The IL-4 response of pro-T cells is not mediated by induction of the interleukin 2 (IL-2)-IL-2 receptor pathway and, unlike IL-2-driven T-cell differentiation, does not require the presence of stromal cells. Taken altogether, these findings suggest that an autocrine IL-4-mediated pathway might be implicated in early thymocyte differentiation-namely, in the generation of T cells bearing the gamma-delta T-cell receptor.