Phorbol-ester-mediated induction and augmentation of mitogenesis and interleukin-2 production in human T-cell lymphoproliferative disease.

The mitogen reactivity of peripheral blood and bone marrow cells from 5 patients with T-cell chronic (T-CLL) and 9 patients with T-ceII acute (T-ALL) Iymphoproliferative disease was investigated. Proliferative responsiveness to phytohemagglutinin (PHA) generally was found to be reduced or completely absent. Stimulation with PHA in the presence of the tumor promoter 1 2-0-tetradecanoyl phorbol-1 3-acetate (TPA). however, resulted in the induction of proliferation in 5/8 PHA nonresponsive patient cell cultures (2/2 T-CLL and 3/6 T-ALL cultures) and augmentation of proliferation in 6/6 patient cultures that were already reactive to PHA itself (3 T-CLL and 3 T-ALL cultures). Under identical conditions, a similar induction and enhancement of mitogenesis was found with normal thymocytes and mature T-ceIl cultures, respectively; the latter, however, only at suboptimal PHA doses. TPAinduced mitogenesis of the group of T-CLL cell populations