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 μM) for 30 min at 37°C show an increase in the percentage of cells expressing receptors for the Fc portion of IgG (RFc γ ) 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 (T R cells) that is enriched for OKT4 + cells. Untreated normal T R cells express helper/inducer cell activity for T-cell-dependent B-cell differentiation, while adenosine-treated T R cells suppress B-cell differentiation. In contrast, in T R cells isolated from patients with systemic lupus erythematosus (SLE), adenosine fails to induce immunosuppressor activity or to increase the percentage of OKT8 + and RFc γ + cells. In addition, although incubation of normal T R cells with adenosine causes a transient increase in cAMP levels (up to 160% of control within 5 min), in SLE T R cells, cAMP levels fall by 50% within 10 min. The photoaffinity label 8-azidoadenosine cyclic [ 32 P]monophosphate has been 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 T R cells, this receptor becomes occupied in response to adenosine. In contrast, in SLE T R cells, no change in cAMP receptor occupancy is detected. Although adenosine has a differential effect on normal and SLE T R cells, cAMP derivatives that can traverse the cell membrane (8-bromo- and 8-azidoadenosine cyclic monophosphates) induce an increase in the RFc γ + cell subset in both normal and SLE T R cells. These results suggest that 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 T R cells may account, in part, for their lack of immunosuppressive activity.

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