Interplay between IL-2 and IL-4 in human thymocyte differentiation: Antagonism or agonism

The effect of recombinant Interleukin 2 (IL-2) and IL-4, as well as a combination of both lymphoklnes on human post-natal thymocytes at different maturation stages, was analyzed by cutturtng highly purified pro-T cells, pre-T cells, double-negative and double-positive thymocyte subsets In the presence of IL-2 and/or IL-4. Both IL-2 and IL-4 responsiveness are develop-mentally regulated In human thymocytes, since IL-2 and IL-4 responses decline with Increasing thymocyte differentiation, double-positive T cells displaying far less proliferation than Immature thymocytes. IL-2 and IL-4 may Influence pro-T cell growth In both an antagonistic and additive fashion. At low doses, IL-4 Inhibits IL-2-supported growth of pro-T cells, whereas, at higher concentrations, this inhibitory effect is masked by the ability of IL-4 to stimulate pro-T cell proliferation. In contrast to peripheral lymphocytes, IL-4 does not down-regulate the expression of the IL-2 receptor light chain on thymocytes. In pro-T cell cultures, IL-2 and IL-4 favour the differentiation of distinct cell populations, namely lymphocytes displaying preferentially a TCR α/β+ and CD4+CD8- phenotype versus predominantly TCR γ/δ+ and CD4-CD8+ cells, respectively. The effect of IL-2 dominates over that of IL-4, since the composition of cultures set up In the presence of IL-2 plus IL-4 resembles that of cells cultured with IL-2 alone. In synthesis, IL-2 and IL-4 exhibit reciprocal inter-relations In human thymocyte cultures, thus supporting the notion that these lymphokines are Implicated In the complex regulation of a local cytokine network.