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 interact with membrane molecules (phytohemagglutinin [PHA], anti-CD3 monoclonal antibody [MAB]) and with the intracytoplasmic protein kinase C (PKC) was investigated in 22 B-CLL patients and 18 healthy controls. 3H-thymidine uptake in T lymphocytes from 14 of 22 B-CLL patients after PHA, anti-CD3, and phorbol myristate acetate (PMA) was found to be lower than in the healthy controls. This defective proliferative response was not corrected by the exogenous addition of interleukin-2 (IL-2) to the 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 and that it was normalized after 5 days of culture. Defective response of T lymphocytes from B-CLL patients to polyclonal mitogens was observed in those patients with advanced disease (stages A, B, and C). However, this T cell proliferative response was normal in patients with "smoldering B-CLL." We conclude that the defective proliferative response to membrane and intracytoplasmatic mitogenic signals on T lymphocytes from a part of B-CLL patients can be ascribed to delayed activation and cell-cycle progression, and an association between the alterations in the T cell compartment of B-CLL patients and the progression of the disease may be suggested.