Activation of the interleukin 2 pathway precedes CD3-T cell receptor expression in thymic development. Differential growth requirements of early and mature intrathymic subpopulations.

T cell activation induced via the CD3-T cell receptor (TcR) complex, or by triggering of polyclonal antigen-independent pathways, involves both interleukin 2 (IL 2) production and IL 2 receptor (IL 2R) expression and results in T cell proliferation. To assess the potential role of the IL 2 pathway in T cell development, growth and activation requirements of intrathymic T cell precursors were analyzed and correlated with the expression of IL 2R. In contrast to CD3-TcR+ (either CD4+ or CD8+) mature thymic cells, CD3-TcR- CD1-4-8- early prothymocytes constitutively expressed IL 2R and displayed IL 2-mediated proliferation, which was inhibited by anti-IL 2R monoclonal antibodies (mAb). Moreover, prothymocytes developed spontaneous proliferation in the absence of exogenous IL 2, which was also abrogated by blocking of IL 2R with specific mAb. The possibility that both IL 2 production and IL 2R expression are autonomously activated early in T cell development, before acquisition of the CD3-TcR complex, led us to study the implication of alternative pathways of activation at this ontogenic stage. Triggering of the CD2 pathway with mAb against two different epitopes of the molecule (D66 and 9.6/T11(1) induced proliferation of CD3-TcR- prothymocytes in the absence of exogenous IL 2, while proliferation of CD3-TcR+ mature thymocytes required Il 2 supplementation. These data suggest that polyclonal activation of the Il 2 pathway may be selectively operative at early stages of T cell development, being involved in the growth and differentiation of intrathymic T cell precursors.