MODULATION OF HUMAN T-CELL FUNCTIONS BY SURFACE SULFHYDRYL-GROUPS - DIFFERENTIAL-EFFECTS ON IL-2 PRODUCTION AND RESPONSIVENESS

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cel ls prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaire d cellular responsiveness to exogenous IL-2. Studies using MoAbs indic ated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH gr oups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lympho ma cell line. The data are consistent with the hypothesis that sulphyd ryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol ident ified on the IL-2 receptor may be a candidate for oxidation on cells f rom patients with chronic inflammatory diseases such as rheumatoid art hritis and thus contribute to the aberrant function of T cells in thes e patients.