Glutathione Augments in Vitro Proliferative Responses of Lymphocytes to Concanavalin A to a Greater Degree in Old than in Young Rats

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Abstract
The proliferative response of splenocytes to concanavalin A (Con A) is significantly lower in aged than in young rats. The addition of reduced (GSH) but not oxidized (GSSG) γ-glutamylcysteinylglycine (glutathione) in vitro totally reverses the defective proliferative response of splenocytes from aged rats. The inhibitor of γ-glutamylcysteine synthetase, buthionine sulfoximine, abrogates the in vitro proliferation of splenocytes from young rats activated with Con A, and this effect is significantly reversed by addition of GSH. The enhancing effects of GSH on proliferation of Con A-activated splenocytes of both young and old rats are apparent as early as 24 h and are still evident as late as 72 h in culture. Both cysteine and 2-mercaptoethanol are able to mimic the effect of GSH in causing a greater increase in Con A-induced proliferative responses of splenocytes from old rats (eightfold) as compared to young animals (threefold). Although 2-mercaptoethanol increases expression of membrane-bound transferrin receptors on both Con A-activated splenocytes and T lymphocytes, this alone does not account for the greater enhancement of Con A-induced proliferation of splenocytes from old as compared to young rats. These data are consistent with the hypothesis that the glutathione peroxidase-dependent detoxification system is defective in T lymphocytes of aged rats.