The effect of intensive immunosuppression on the in vitro activity of lymphocytes from multiple sclerosis patients.

During a small clinical trial of intensive immunosuppression in multipel sclerosis (MS, 14 patients) the changes of in vitro lymphocyte responses to mitogens were followed. A variable depression of the normal responses to phytohaemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was seen in the patinets during the inital week of treatment with prednisone (150 mg/day tapered to 20 mg/day by day 7), and azathiprine (3 mg/kg daily). They were further depressed during antilymphocyte globulin therapy (ALG 500 mg/day on weekdays, weeks 2-5 of treatment). These responses returned rapidly to the lower normal range after the three weeks of ALG despite the continued prednisone and azathipprine therapy. A complex effect of immunosuppression on lymphocyte subpopulations was suggested by three findings. Firstly, in contrast with the reduction in response to plant mitogens no lowering of the response to allogeneic lymphoid cell line cells (LCL) was seen during the first week of treatment. Secondly, some patinets, particularly those expressing the HLA-7 antigen, had a low pre-treatment response to LCL which showed an improvement during treatment and which was maintained through the first week of ALG treatment. Thirdly, single inviduals sometimes showed different degrees of suppression of different responses during and after ALG treatment. Occasionally, responses showed some recovery even during the ALG treatment, suggesting that higher ALG doses were required in these patients. The results suggest that the action of immunosuppressive drugs on lymphocyte activity differs between individuals due to the heterogeneity of the lymphocyte subpopulations present.