Tryptophan Catabolism and Regulation of Adaptive Immunity

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Abstract
Progress in elucidating cellular, molecular, and biochemical processes that regulate immune responses provides increasingly plausible explanations for the normal status of tolerance to self Ags that guards most humans from Ehrlich’s imagined horror autotoxicus (1). Emerging data on regulatory T cells (Tregs)2 and regulatory APC (APCregs) provide fertile ground for resolving some perplexing immunological paradoxes. (2, 3, 4). Thus, most people harbor potentially autoreactive T and B cells without suffering autoimmune diseases. This situation is reminiscent of the paradox of pathogen and tumor persistence in immunocompetent hosts. Unresponsiveness in these situations is puzzling, raising hopes that immunotherapeutic interventions might reverse tolerance. Tregs and APCregs may be the culprits in these cases, perhaps exploited by mechanisms evolved by pathogens, or acquired by tumors, to protect them from host immunity. Tumor survival and pathogen persistence in immunocompetent hosts has a counterpart in mammalian reproduction. Fetal tissues that express paternally inherited genes (foreign to the mother) are tolerated by the maternal immune system despite intimate association between maternal and fetal tissues during gestation. Recent reviews on Tregs and APCregs (cited above) provide excellent summaries of progress to elucidate their roles in immunoregulatory processes. However, molecular mechanisms underlying immunoregulatory phenomena remain elusive.