Splenocyte glutathione and CD3-mediated cell proliferation are reduced in mice fed a protein-deficient diet

Protein-energy malnutrition (PEM) is associated with decreased host immune defense. Glutathione (GSH) status is reported to be decreased in PEM, and GSH is important for lymphocyte function. The objective of the present study was to investigate the effects of PEM and dietary repletion (RP) on GSH status in various tissues and splenocytes and on CD3-mediated calcium mobilization and cell proliferation of splenic T-lymphocytes. For the PEM model, mice were fed a 0.5% protein diet (LP group) for 4 or 6 wk, and control mice were fed a 15% protein diet (CP group). In the RP study, LP mice were fed the 15% protein diet for 3 d, 1 wk, 2 wk or 3 wk (RP groups). Glutathione concentrations were significantly lower in liver, lung, heart and spleen of LP mice compared with CP mice at 4 and 6 wk. Splenocytes from LP mice were significantly lower in number and had a lower intracellular GSH concentration, depressed CD3-stimulated T-lymphocyte proliferation in culture media without thiol supplementation (2-mercaptoethanol), and enhanced CD3-stimulated proliferation in thiol-supplemented culture media compared with splenocytes from CP mice. CD3-stimulated calcium mobilization was significantly lower in CD8+, but not CD4+, splenocytes from LP mice. Within 1 wk of dietary repletion, splenocyte GSH concentration was normal and splenocyte numbers were greater, and in vitro sensitivity of CD3-stimulated T-lymphocyte proliferation to thiol was lower, compared with LP mice. Glutathione status in vivo and thiol supplementation in vitro seem to modulate the signal transduction pathway for T-lymphocyte proliferation in mice with PEM.