Abnormal adenosine-induced immunosuppression and cAMP metabolism in T lymphocytes of patients with systemic lupus erythematosus

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Abstract
Normal human T lymphocytes incubated with adenosine (10 .mu.M) for 30 min at 37.degree. C show an increase in the percentage of cells expressing receptors for the Fc portion of IgG (RFc.gamma.) and the OKT8 antigen, while the proportion of OKT4+ cells decreases. These effects occur exclusively in a subset of T cells with theophylline-resistant sheep erythrocyte receptors (TR cells) that is enriched for OKT4+ cells. Untreated normal TR cells express helper/inducer cell activity for T-cell-dependent B-cell differentiation, while adenosine-treated TR cells suppress B-cell differentiation. In TR cells isolated from patients with systemic lupus erythematosus (SLE), adenosine fails to induce immunosuppressor activity or to increase the percentage of OKT8+ and RFc.gamma.+ cells. Although incubation of normal TR cells with adenosine causes a transient increase in cAMP levels (up to 160% of control within 5 min), in SLE TR cells, cAMP levels fall by 50% within 10 min. The photoaffinity label 8-azidoadenosine cyclic [32P]monophosphate was used to show that human T lymphocytes have a single cAMP receptor site that appears to be the regulatory subunit of type I protein kinase. In normal TR cells, this receptor becomes occupied in response to adenosine, while in SLE TR cells, no change in cAMP receptor occupancy is detected. Although adenosine has a differential effect on normal and SLE TR cells, cAMP derivatives that can traverse the cell membrane (8-bromo- and 8-azidoadenosine cyclic monophosphates) induce an increase in the RFc.gamma.+ cell subset in both normal and SLE TR cells. Apparently, cAMP mediates the effects of adenosine on cell surface markers of T lymphocytes. The lack of an adenosine receptor-coupled adenylate cyclase activity in SLE TR cells may account, in part, for their lack of immunosuppressive activity.