Abstract
Several T [thymus-derived] cell clones were derived by limiting dilution of secondary mixed leukocyte culture cells stimulated by H-2- and M locus (Mls)-disparate [mouse] spleen cells. When examined for the expression of cytolytic activity and the ability to proliferate, these cell clones could be classified into 2 major categories. One type of cell was noncytolytic; when cultured with irradiated spleen cells, such clones proliferated in response to Mls determinants. Some, but not all, of these clones expressed Lyt-1 alloantigens. The other type of cell was cytolytic; these clones did not proliferate when cultured with irradiated allogeneic spleen cells unless supernatant fluid (SF) was added. These cytolytic clones expressed Lyt-2 alloantigens. Some cytolytic clones were specific for H-2Kd and others for H-2Dd alloantigens. Still other cytolytic cell clones exhibited cross-reactive lysis of different H-2-bearing tumor and Con [concanavalin] A blast target cells. Noncytolytic T cell clones, when stimulated by Mls antigens, were examined for their ability to promote proliferation of cytolytic T cell clones. All of the noncytolytic cell clones tested promoted proliferation of cytolytic cell clones with the concomitant expression of cytolytic activity directed toward the original stimulating alloantigen (H-2d). Amplification of cytolytic activity was dependent upon stimulation of the noncytolytic amplifier T cell clones by Mls antigens. Specific alloantigen (signal 1) was not required for proliferation of the cytolytic cell clones; the amplifying signal (signal 2), delivered by the amplifier cell clones, was sufficient alone to promote proliferation of the cytolytic cell clones. Whereas proliferation of the amplifier cells was radiosensitive, the generation of the soluble amplifying signal was radioresistant. Amplification of cytolytic activity was observed when amplifier cells were physically separated from responding cytolytic cells in Marbrook cultures or when cytolytic cells were cultured with SF collected from amplifier cell cultures. The amplifying factors were neither antigen-specific nor strain-specific and could be produced by Lyt-1- cells. The availability of cloned T cell lines that retain specific biological function offers unique opportunities to characterize cell surface proteins and cell-cell interactions.