Stimulation of T-cell proliferation by pancreastatin and its C-terminal fragment (33-49)

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(-8) M they exhibit a dose-dependent stimulatory effect on concanavalin A-induced response with the maximal effect at 10(-8) M concentration. They were inactive in response to a B-cell mitogen, lipopolysaccharide, 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(-9) M) 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.