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.
Prieto
A
A
Servicio de Hematologia, Universidad de Alcalá de Henares, Madrid, Spain.
Garcia-Suarez
J
J
Reyes
E
E
Lapeña
P
P
Hernandez
M
M
Alvarez-Mon
M
M
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D014316:Tritium; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine