Regulation of human T lymphocyte surface antigen mobility by purinergic receptors.
The present study was undertaken to establish whether the capping mechanism of normal human T lymphocytes is regulated by a purinergic receptor. Interaction of T lymphocytes with adenosine significantly increased the mobility of the T3, T4, and T8 surface antigens. This enhanced rate of capping was reflected by a significant decrement in the time intervals to achieve half-maximal capping. T lymphocytes preincubated with theophylline or isobutylmethylxanthine did not exhibit accelerated capping or a decrease in the time required for half-maximal capping in response to adenosine, suggesting that these agents inhibited the binding of adenosine to its receptor. A role for a cAMP-dependent pathway in capping was suggested by the observation that the phosphodiesterase inhibitor RO-201724 caused a decrease in the concentration of adenosine required to accelerate the capping process. Moreover, exposure of T lymphocytes to the cyclic nucleotide derivatives 8-N3-cAMP and 8-Br-cAMP mimicked the effect of adenosine, significantly reducing the time to half-maximal capping. Photoaffinity labeling of intracellular cAMP receptors with 32P-8-N3-cAMP indicated that adenosine caused occupancy of the receptors. This effect of adenosine was inhibited by theophylline, a known purinergic receptor blocker. The data support the concept that the T cell capping mechanism is mediated by an adenylate cyclase-coupled purinergic receptor that activates a cAMP-dependent pathway, and that this pathway is functional in the T3+, T4+, (inducer) and T3+, T8+ (suppressor) subsets.
D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D000954:Antigens, Surface / Q000032:analysis*; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006801:Humans; D007152:Immunologic Capping / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011983:Receptors, Purinergic; D013601:T-Lymphocytes / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D000954:Antigens, Surface; D010726:Phosphodiesterase Inhibitors; D011948:Receptors, Antigen, T-Cell; D011953:Receptors, Cyclic AMP; D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D013806:Theophylline; D000242:Cyclic AMP; D000241:Adenosine