Human Lymphocyte Response to Phytomitogens in Vitro: Normal, Agammaglobulinemic and Paraproteinemic Individuals

Abstract Studies of the time course of thymidine incorporation during stimulation of lymphocytes from normal individuals with four plant mitogens over a 10-day period demonstrate several differences in response profiles. Whereas the peak responses for cultures stimulated with phytohemagglutinin (PHA), wax bean glycoprotein and concanavalin A (Con A) occurred at 3 or 5 days, the lower peak response to pokeweed mitogen (PWM) was observed at 5 or 7 days. Cultures stimulated with PHA, wax bean glycoprotein and PWM continued to show significant thymidine incorporation at 7 and 10 days, although the response to Con A had returned to baseline after 7 days. Lymphocytes from eight adult “acquired” agammaglobulinemic patients and their four available parents had a diminished thymidine incorporation in 3-day cultures using each of the four mitogens (p < 0.001). A late response was observed with PHA or wax bean stimulation at 5 to 7 days, comparable to controls at 3 days. With Con A, lymphocytes from both the “acquired” agammaglobulinemic patients and their parents had a diminished incorporation throughout the 10-day period (p < 0.001). Stimulation with PWM distinguished the lymphocytes of the patients from their heterozygous parents; at 5 to 7 days the parents had a peak comparable to controls, whereas the “acquired” agammaglobulinemics had a diminished peak (p < 0.001) at 10 days. Lymphocytes from patients with multiple myeloma and Waldenström's macroglobulinemia had diminished thymidine incorporation in response to Con A during a 10-day incubation period. These patients had normal or late responses comparable in magnitude to controls with PHA, wax bean glycoprotein and PWM. These observations suggest that plant mitogens have selective and specific actions on lymphocyte subpopulations. Differences in the time course and magnitude of lymphocyte response to plant mitogens may reflect different circulating subpopulations of cells or alterations in the total number of cells responsive to mitogen. Detailed time studies using several mitogenic agents represent a possible approach to the assessment of lymphocyte function in immunologic diseases.