DIMINISHED DNA-SYNTHESIS IN T-CELLS FROM B CHRONIC LYMPHOCYTIC-LEUKEMIA AFTER PHYTOHEMAGGLUTININ, ANTI-CD3, AND PHORBOL-MYRISTATE ACETATE MITOGENIC SIGNALS

T lymphocytes from patients with B cell chronic lymphocytic leukemia ( B-CLL) exhibit defective proliferative response to plant lectins. The blastogenic response of purified T lymphocytes to signals that interac t with membrane molecules (phytohemagglutinin [PHA], anti-CD3 monoclon al antibody [MAB]) and with the intracytoplasmic protein kinase C (PKC ) was investigated in 22 B-CLL patients and 18 healthy controls. H-3-t hymidine uptake in T lymphocytes from 14 of 22 B-CLL patients after PH A, anti-CD3, and phorbol myristate acetate (PMA) was found to be lower than in the healthy controls. This defective proliferative response w as not corrected by the exogenous addition of interleukin-2 (IL2) to t he culture medium. In analyzing the cell cycle progression of these T lymphocytes from B-CLL patients, we found that the percentage of cells in S phase at 2 days of PHA stimulation was significantly decreased a nd that it was normalized after 5 days of culture. Defective response of T lymphocytes from B-CLL patients to polyclonal mitogens was observ ed in those patients with advanced disease (stages A, B, and C). Howev er, this T cell proliferative response was normal in patients with ''s moldering B-CLL.'' We conclude that the defective proliferative respon se to membrane and intracytoplasmatic mitogenic signals on T lymphocyt es from a part of B-CLL patients can be ascribed to delayed activation and cell-cycle progression, and an association between the alteration s in the T cell compartment of B-CLL patients and the progression of t he disease may be suggested.