Cellular origins of co-stimulator (IL2) and its activity in cytotoxic T lymphocyte responses.

Abstract

Abstract Production of co-stimulator (Interleukin 2, IL2), a Con A-induced lymphokine, requires participation of two cell types: T lymphocytes and non-T cells that adhere to nylon wool, presumably macrophages. The T cells bear the lymphocyte differentiation antigens Ly 1.1, Ly 5.1, and Ly 7.2, but not Ly 2.1 or Ly 6.1. T cells that are “helpers” in the CTL response have the same Ly pheno-type. The requirement for adherent cells is met by using macrophages cultured from bone marrow or the macrophage product LAF (IL1). Co-stimulator acts as a second signal in immune induction of T cell precursors, the first signal being provided by antigens or mitogens. It allows the proliferation of thymocytes cultured at low cell density in response to Con A. It stimulates the generation of cytotoxic T lymphocytes (CTL) from thymocyte precursors, and restores the response of splenic precursors that have been depleted of helper cells by treatment with anti-Ly 7.2 serum. Co-stimulator appears to replace T helper cells in the antibody response of B cells to sheep erythrocytes, in this way resembling T cell-replacing factor. It also restores the CTL response of lymph node lymphocytes that have been depleted of adherent cells. Thus, co-stimulator is a product of interaction between adherent cells (macrophages) and T helper cells, and it replaces both of these in proliferative or immune responses by T cells. The factor does not bear Ia antigens, and it is not H-2 restricted; this distinguishes it from allogeneic effect factor (AEF).