Modulation of T cells by cyclic AMP in murine influenza virus infection. I. In vitro inhibition of cytotoxic T lymphocytes by exogenous cyclic AMP analogues and by agents which increase intracellular cyclic AMP concentrations

The effects of 8-bromo-cyclic AMP and cyclic AMP agonists (cholera toxin plus hydrocortisone and prostaglandin E2 plus 3-isobutyl-1-methylxanthine) on the cytotoxic activity of T cells generated during murine influenza virus infection have been examined. Treatment of influenza A/WSN virus primed primary immune spleen cells and their cultured secondary effector T cells from Balb/c mice with these agonists resulted in increases in cyclic AMP levels. These agents also had a marked inhibitory effect on the cytotoxic activity of primary immune spleen cells, but a much weaker inhibitory effect on that of secondary effector T cells. No significant effect of 8-bromo-cyclic GMP on the cytotoxic activity of these two cell types was observed. The cytotoxic activity of H-2-restricted, virus-specific T cells generated either in vivo (primary) or in vitro (secondary) was not significantly inhibited by treatment with histamine, whereas that of alloreactive killer T cells generated in vivo was markedly inhibited. These results suggest that the actions of H-2-restricted, virus-specific T cells may not be regulated by histamine during viral or inflammatory processes.