Spontaneous "in vitro" variations of theophylline sensitivity in human peripheral blood lymphocytes

Theophylline reversibly inhibits E rosette formation by a portion of human circulating T lymphocytes. We investigated the effect of theophylline on E rosette formation and intracellular content of cyclic nucleotides (cAMP, cGMP). When the amine is added to 15 human healthy donors' lymphocytes either before or after 24 hours of culture at 37 degrees C, in absence of mitogens, a portion of theophylline-sensitive T cells spontaneously becomes theophylline-resistant after 24 hours of culture. While the intracellular content of cAMP does not significantly vary, the ability of theophylline to induce an increase of cAMP appears to be impaired after 24 hours of culture. The possible correlation between theophylline resistance and impaired turnover of cAMP in the cultured lymphocytes is discussed.