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Adenosine induced immunosuppression: The role of the adenosine receptor-adenylate cyclase interaction in the alteration of T-lymphocyte surface phenotype and immunoregulatory function

1986; Elsevier BV; Volume: 8; Issue: 3 Linguagem: Inglês

10.1016/0192-0561(86)90115-3

1879-3495

Ruth E. Birch, Stephen H. Polmar,

Transplantation: Methods and Outcomes

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)