STIMULATION OF RAT LYMPHOCYTE PROLIFERATION BY HYDROCORTISONE DURING THE INDUCTION OF CELL-MEDIATED IMMUNITY IN VITRO

SUMMARY The effect of hydrocortisone on a cell-mediated reaction was studied by using a model system in which rat lymph node cells are sensitized against and destroy mouse fibroblasts in vitro. During the first 72 hr of sensitization, specifically reactive lymphocytes remain intact while lymphocytes which do not recognize the sensitizing fibroblasts die and are eliminated. Following this quiescent stage, the sensitized lymphocytes proliferate, and specific effector lymphocytes appear during the next several days of culture. In earlier studies we found that hydrocortisone increased the proportion of specifically sensitized lymphocytes by enhancing the elimination of unreacting lymphocytes. In the present studies we investigated the effects of hydrocortisone on the proliferation of sensitized lymphocytes. The following conclusions were derived. (1) Hydrocortisone enhances lymphocyte multiplication by acting during the quiescent stage. Proliferation is not affected by adding hydrocortisone during the proliferation stage itself. In addition, the replication of sensitized lymphocytes does not require the continued presence of the antigen-specific sensitizing fibroblasts. (2) Treatment of lymphocytes with hydrocortisone for 1 hr before their contact with sensitizing fibroblasts is sufficient to augment the proliferation of the sensitized lymphocytes. (3) These effects of hydrocortisone are not directly related to the degree of lymphocyte elimination. Thus, in addition to eliminating unreacting lymphocytes, hydrocortisone can facilitate cell-mediated immunity by enhancing the proliferation of sensitized lymphocytes. This finding raises important questions regarding the clinical use of glucocorticoids as immunosuppressive agents in cell-mediated immune reactions.