We have studied the effect of pancreastatin and its C-terminal fragment (33–49) on mitogen-stimulated T lymphocyte proliferation. In a concentration range from 10–12 to 10–8M they exhibit a dose-dependent stimulatory effect on concanavalin A-induced response with the maximal effect at 10–8M concentration. They were inactive in response to a B-cell mitogen, lipopolysaccha-ride, which points to an involvement of T but not B lymphocytes in their response. Pancreastatin can still produce a stimulatory effect when added 18 h after incubation of cultures with concanavalin A and apparently uses a diacylglycerol independent mechanism. When cells were preincubated for 4, 16 or 24 h with pancreastatin or its fragment and then stimulated with concanavalin A, a ten times lower concentration of peptides was needed (10–9M) to obtain the maximal response. This suggests that resting cells are more sensitive to pancreastatin and its fragment. Both peptides exhibit a very similar pharmacological profile, indicating that the C-terminal part of the molecule is responsible for the effect on T-cell proliferation.

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