Early cellular responses to mitogens and adjuvants in the mouse spleen.

The purpose of this study was to evaluate the cellular events in the spleens of mice following the intravenous injection of mitogens and adjuvants. The compounds used were concanavalin A, polyadenylic polyuridylic acid, beryllium sulfate, bacterial endotoxin, tuberculin-purified protein derivative, and dextran sulfate. Nine different strains of mice (some deficient in the C5 component of complement) received a single dose of these compounds, and their spleens were studied at sequential time intervals, ranging from 1 hour to 14 days. Concanavalin A triggered marked blast activity in the T cell zones of the splenic white pulp which was maximal at 24 hours following the injection. -3H-thymidine incorporation increased significantly, but the number of immunoglobulin-negative cells did not increase, probably because of a concomitant loss of hematopoietic cells. Polyadenylic polyuridylic acid and beryllium sulfate produced an increase in the number of lymphocytes in the T cell zones by 12 to 24 hours, but mitotic activity was unremarkable. None of the above T cell zone changes was observed in neonatally thymectomized mice. Endotoxin, purified protein derivative, and dextran sulfate produced marked B cell zone hyperplasia. Similar histologic changes were seen in the thymectomized animals. -3H-thymidine incorporation and number of immunoglobulin-positive cells were significantly increased by 24 hours. Endotoxin and dextran sulfate in some strains of mice caused marked depletion of the T cell zones. The effects of concanavalin A, endotoxin, and dextran sulfate were unrelated to the presence or absence of C5 protein. These experiments show that (1) concanavalin A, bacterial endotoxin, tuberulin-purified protein derivative, and dextran sulfate trigger in vivo the same cellular components of the immune system as they do in vitro; (2) polyadenylic polyuridylic acid and beryllium sulfate may influence the immune system by increased localization of lymphocytes in the T cell zones.