I. Regulation and Control of Immune Responses: A. Production and characterization of T cell differentiation factor (TCDF). TCDF was produced in syngeneic lymphocyte-macrophage culture. The production of TCDF required the recognition of self Ia on macrophages, and the presence of L3T4 cells. In addition to interleukin 2 (IL2), TCDF was also needed to induce the differentiation of mitogen-activated CTL (cytotoxic T lymphocytes) into CTL effectors. Upon separation by Sephadex G100 gel filtration, the peak TCDF activity was at 16,000 dalton mw, which was distinct from IL2 whose peak activity was at 30,000 dalton. B. Regulation of the cytotoxic activity of alloreactive CTL by helper cells and lymphokines. Transferring donor cells from allo-CTL generated in unseparated mixed lymphocyte culture (MLC) into host culture (HC) containing syngeneic lymphocytes and macrophages resulted in the generation of allo-CTL of donor origin. In contrast, transferring cultured cells generated in Lyt2-depleted MLC into HC resulted in the generation of allo-CTL of host origin. Two different helps were identified here. Antigen nonspecific help was generated in the host culture, and antigen specific help was generated in Lyt2-depleted MLC. Both required L3T4 cells. II. Tumor Immunology: LICC (lymphokine-induced cytotoxic cells) or LAK (lymphokine-activated killer) cells were generated by culturing normal spleen cells with syngeneic macrophages and indomethacin, or by culturing normal spleen cells with exogeneous IL2. The precursors of LICC were Thyl-, Asialo GM1+, Lyt2- and thus were NK-like cells. The effectors were Thyl+, Asialo GMl-, Lyt2- and thus were neither classical NK cells nor classical CTL. LICC selectively killed lymphoid and tumor targets of different etiological origin, and these cells might represent an important alternate host defense mechanism against tumor growth.
