Contrasting effects of prostaglandin E 2 and indomethacin in modulating con A-induced human lymphocyte proliferation and suppressor cell development

Abstract

Several chronic diseases that are characterized by depressed Con A-induced suppressor cell activity are also noted to exhibit depressed in vitro blastogenic responses to mitogens. We investigated the relationship between these two parameters to determine whether depression of lymphocyte proliferation would result in depressed suppressor cell function. First, a correlation in time was found between the degree of initial Con A-induced lymphocyte proliferation and subsequent suppressor development. Second, mitomycin C treatment of Con A-activated cells while preventing further blast cell proliferation, was found not to prevent their suppressor cell function. Third, inhibition of lymphocyte blastogenesis with physiological concentrations of prostaglandin E 2 was also associated with depressed suppressor cell generation. Finally, enhancement of initial lymphocyte proliferation with indomethacin added in vitro resulted in a significant increase in suppressor cell activity. This enhanced response was nullified in the presence of exogenous prostaglandin E 2. These observations strongly suggest that maturation of lymphocytes into blast cells is an important event in the generation of suppressor cells. In addition, these results suggest that caution be taken in interpreting results of Con A suppressor assays in patients with either depressed in vitro mitogen reactivity or in patients taking nonsteroidal anti-inflammatory drugs.