Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness

Abstract

SUMMARY 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 cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclcar cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl 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 identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.