Alteration of lymphocyte response by sulfhydryl and disulfide compounds

The effects on the proliferative response of human lymphocytes of the sulfhydryl agents d -penicillamine and 5-thiopyridoxine, some analogues of these agents, and their respective disulfides were investigated. The sulfhydryl agents inhibited the proliferation of mitogen-stimulated lymphocytes and suppressed the mixed lymphocyte reaction (MLR) in one-way mixed lymphocyte cultures (MLC). The inhibition in both systems was partial and dose dependent. Prolonged preincubation of responder cells with these sulfhydryl agents, followed by their removal prior to MLC, resulted in enhancement of DNA synthesis. Pretreatment of the stimulator cells was without effect. Analysis of the incubation mixtures of the sulfhydryl compounds showed that they had undergone disulfide formation. Disulfide compounds enhanced DNA synthesis in both mitogen-stimulated cultures and in MLC. The enhancement was dose dependent and limited in concentration range. Preincubation of lymphocytes with disulfides also resulted in enhancement of DNA synthesis when these cells were stimulated with PHA or used as responder cells in one-way MLC. Similar treatment of stimulator cells was without effect. The ability of lymphocytes to form rosettes with sheep erythrocytes was not altered by sulfhydryl agents or their disulfide derivatives.