In vitro correction of antigen-induced immune suppression: Effects of histamine, dibutyryl cyclic AMP and cholera enterotoxin

Reduced immune response potential of SJL/J mouse spleen cells to the synthetic polypeptide poly (l Tyr,lGlu)-poly l Pro-poly l Lys [(T,G)-Pro-L]was observed when the spleen cells were incubated in vitro with (T,G)-Pro-L prior to in vivo challenge of the cells with the same antigen in syngeneic, irradiated recipients. Incubation of the cell-antigen mixture in the presence of histamine, prostaglandins E₁ and F_2α, dibutyryl cyclic AMP, or cholera enterotoxin abrogated the antigen-induced loss of responsiveness. The immunological effects of histamine, prostaglandins, and cholera enterotoxin were associated with increased accumulation of cyclic AMP in the spleen cell suspension. Addition of the histamine antagonist diphenhydramine or anti-cholera toxin to the respective in vitro incubation mixtures abolished the effects of histamine and cholera enterotoxin on both the immune response and increased cyclic AMP levels. These results suggest that this type of antigen-induced immunosuppression can be reversed by pharmacological agents which elevate levels of cyclic AMP.