Protease potentiation of thymocyte blastogenesis.

When rat thymocytes were cultured with concanavalin A (con A), addition of trypsin increased the incorporation of [H]-thymidine (H-TdR) several fold over that observed with mitogen alone. The potentiating effect of trypsin was greatest with suboptimal concentrations of mitogen, less with optimal, and least with superoptimal concentrations. Trypsin also increased blastogenesis and stimulated [H]-leucine incorporation into thymocyte proteins. Thymocytes cultured with trypsin in the absence of mitogen sometimes showed increased H-TdR incorporation but the increase was usually small and not consistent. The potentiating action of trypsin is due to its proteolytic activity since it was completely blocked by soybean trypsin inhibitor. Elastase, α-chymotrypsin, and subtilisin also potentiated the action of con A, while papain, collagenase, thrombin, and plasmin had either very little or no effect. Trypsin potentiated H-TdR incorporation into thymocytes cultured in serum-free or serum-supplemented media, but its effects were usually greater in media supplemented with 5% autologous serum. Although heating serum at 56° for 0.5 or 2 h markedly reduced stimulation by con A, the effects of trypsin were greater in media supplemented with heated serum. The possible physiological significance of the results was discussed with respect to protease secretion by macrophages and lymphocyte—macrophage interactions.