Increased responsiveness to adenosine 3'5'-cyclic monophosphate-active agents during the immune response in vivo

Cytotoxic T lymphocytes (CTL) were generated in the spleen following immunization of C57BL/6 mice with allogeneic cells. The activity of such CTL was inhibited by agents that increased intracellular adenosine 3'5',-cyclic monophosphate (cAMP) levels. During the primary immune response, the susceptibility of CTL to inhibition by theophylline remained constant, but susceptibility to histamine, prostaglandin E2 (PGE2). dibutyryl cAMP, and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro-20-1724) increased significantly. The pattern of increased inhibition by histamine differed from that of the other agents. Increased cAMP responsiveness of CTL resulted from at least two distinct biochemical events, possibly including 1) increased receptors and/or increased receptor-adenylate cyclase coupling (for histamine); and 2) increased efficiency of a post cAMP pathway (for dibutyryl cAMP, PGE2, and Ro 20-1724).