Cortisone As a Probe for Cell Interactions in the Generation of Cytotoxic T Cells

Abstract

Abstract The effect of cortisone on the in vitro cell-mediated cytotoxic response was investigated with respect to the participating cell types, viz., the cytotoxic T cell precursor (CTP), the helper cell, and the accessory (A) cell. Spleen and thymus cells from cortisone-treated CBA/CaJ mice were unable to generate alloreactive cytotoxic T cells when cultured with semiallogeneic (CBA/CaJ × DBA/2JF1) spleen cells or allogeneic (P815) tumor cells. This immunosuppression could be reversed by the addition of 2-Me to the cultures, which suggests that the CTP and helper cells were present but unresponsive. Measurements of the CTP frequency and helper activity in cultures containing 2-Me confirmed this possibility. Thus, limiting dilution analysis of spleen and thymus cells from cortisone-treated mice showed that they contained higher frequencies of CTP than cells from normal mice. Helper cell activity, as measured by the secretion of helper factor by primed cells, was found to be higher after cortisone treatment. The possibility of a defect in A cell function in spleen cells of cortisone-treated mice was suggested by 1) the ability of irradiated peritoneal macrophages to reconstitute the response, and 2) the greatly reduced efficiency of irradiated spleen cells (adherent or nonadherent) from cortisone-treated mice to restore responsiveness to nonadherent, A cell-deficient normal spleen cells. Although cortisone may exert its immunosuppressive effect on helper cells and CTP directly, it is likely that the deficiency in A cell function is at least partially responsible for the unresponsiveness of cortisone-treated cells.