期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：23
页码：7542-7546
DOI：10.1073/pnas.79.23.7542
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Normal human T lymphocytes incubated with adenosine (10 {micro}M) for 30 min at 37{degrees}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 contrast, 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. In addition, 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 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 TR cells, this receptor becomes occupied in response to adenosine. In contrast, 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. 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 TR cells may account, in part, for their lack of immunosuppressive activity.
