EFFECT OF THIOL COMPOUNDS ON LYMPHOCYTES STIMULATED IN CULTURE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 35  (1) , 189-201
Abstract
The effect was studied of D-penicillamine (D-PAm) and other thiol compounds (concentration range, approximately 10-4-3.4 .times. 10-3 M) on mouse spleen cells, stimulated in culture by concanavalin A or by mixed lymphocyte interaction. Thiols initially enhanced the rate of incorporation of [3H]-thymidine into DNA of these cells. The enhancement was typically followed by a sharp decline in activity to a level often below that of thiol-free cultures. The time which elapsed between adding the thiol and the decline in activity depended on the concentration of the particular thiol used. Exceptional among thiols studied was L-cysteine, which lacked inhibitory properties. Variation of the L-cystine content of the medium used here influenced the effect of thiols such as D-PAm on the cells, an increase in cystine content favoring the retention of high activity. D-PAm reacted slowly with a constituent of the culture medium, causing the latter eventually to lose its capacity to maintain cells. The effects of this reaction were counteracted by adding L-cystine, L-cysteine and certain other thiol compounds. D-PAm combined with L-cystine in the medium to form the mixed disulfide, which evidently could not be utilized by the cells as a source of L-cystine. Deprivation of this essential nutrient accounted for the eventual inhibition of [3H]-thymidine incorporation in cultures exposed to thiols. The initital enhancing effect of thiols on stimulated lymphocytes represented a modulation of the response to the primary stimulant. There was no evidence that thiols were themselves mitogenic.