Adenosine induced immunosuppression: the role of the adenosine receptor--adenylate cyclase interaction in the alteration of T-lymphocyte surface phenotype and immunoregulatory function.
Adenosine (1 microM at 37 degrees C) rapidly modulates the expression of T-lymphocyte surface antigens (OKT4 and OKT8) and Fc gamma receptors, and increases T-suppressor activity for pokeweed mitogen driven in vitro immunoglobulin synthesis. The adenosine induced loss of OKT4 expressed was maximal within 5 min, while increased OKT8 expression developed more slowly; increased Fc gamma expression was maximal at 30 min after initiation of incubation with adenosine. Adenosine, 2-chloroadenosine and adenosine in the presence of nitrobenzylthioinosine (NBTI) induced the decrease in OKT4 expression. In contrast only adenosine induced the enhancement of OKT8 and Fc gamma receptor expression. Neither 2-chloroadenosine, a poorly transported analog, nor adenosine in the presence of the adenosine transport inhibitor NBTI were capable of enhancing OKT8 or Fc gamma receptor expression. Adenosine was shown to cause a rapid biphasic increase in cAMP, while 2-chloroadenosine and adenosine with NBTI induces a prolonged elevation in cAMP. Similarly isoproteranol which induces a sustained elevation in cAMP suppressed the adenosine induced increases in OKT8 and Fc gamma receptor expression. Incubation of T-helper/inducer lymphocytes with 1 microM adenosine for 30 min at 37 degrees C caused the loss of T-helper function; this loss of T-helper activity has previously been shown to result from the activation of T-suppressor cells. The loss of T-helper function was blocked by the simultaneous addition of isobutylmethylxanthine, an R site adenosine receptor antagonist, or NBTI, an adenosine transport inhibitor. Moreover, 2-chloroadenosine could not induce loss of T-helper function.(ABSTRACT TRUNCATED AT 250 WORDS)
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011983:Receptors, Purinergic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D013806:Theophylline; D000262:Adenylyl Cyclases; D000241:Adenosine; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine