Modulation of human T cell functions by surface sulphydryl 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 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 mononuclear 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.
Smith
S
S
Bath Institute for Rheumatic Diseases, University of Bath, England.
Brown-Galatola
C H
CH
Hall
N D
ND
D001172:Arthritis, Rheumatoid / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013438:Sulfhydryl Compounds