Interleukin 1 can replace the requirement for I-A-positive cells in the proliferation of antigen-primed T cells

Antigen-primed T cells have been shown to require I-region-compatible adherent cells, as well as the priming antigen, to proliferate in vitro. We postulated that the Ia-recognition event is required for the T cell to induce secretion of the monokine interleukin 1 (IL 1) from adherent cells; the conventionally held view is that Ia is directly required for T cell activation. Our hypothesis predicts that IL I could replace the requirement for Ia+ cells in T cell proliferation assays in vitro. To test this prediction, we depleted keyhole limpet hemocyanin (KLH)-primed C57BL/6 mouse lymph node cells of I-A+ cells by treating with monoclonal anti-I-Ab and complement. As expected, this treatment eliminated the ability of KLH to provoke a proliferative response by primed T cells. Proliferation was restored by providing exogenous IL 1, but only in conjunction with added KLH. The proliferative response of primed T cells could also be blocked by adding anti-I-Ab to culture, and this inhibition could similarly be reversed by providing IL 1 in the presence of the specific antigen KLH. On the basis of these findings we propose a model of T cell activation and discuss its implications.