Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes

Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low prolife rative potential both in vivo and in vitro. Here, we have identified that t he capacity of antigen-presenting cells to release cysteine upon receptor-l igand interactions represents a critical parameter for proliferation of LP- Ts. The availability of cysteine is limiting for the intracellular producti on of glutathione, which in turn is essential for cell cycle progression Wh en cysteine is provided either directly or by addition of the reducing agen t 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocy tes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cystei ne, and thereby secure physiological unresponsiveness to antigen exposure i n the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.