Extrathymic T cell differentiation and role of hepatic sinusoids

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There exists a considerable number of unique T lymphocytes in the periphery in congenitally athymic nude mice, and in aged humans and animals with the in-voluted thymus. It is, therefore, suggested by several investigators that the extrathymic pathway of T cell differentiation may be present somewhere. We have recently demonstrated that such extrathymic T cell differentiation occurs in the hepatic sinusoids in humans and mice. This pathway of T cell differentiation resides phylogenetically earlier than the intrathymic pathway of T cell differentiation. Before and after thymic development, extrathymic T cells might work as the surveillance system for atypical cells generated in vivo by virtue of their autoreactivity. Extrathymic T cells have alpha beta TCR (and gamma delta TCR) of intermediate intensity and contain many auto-reactive T cell clones. The existence of the hepatic pathway could clearly explain the phenomenon "breakdown of self-tolerance", and occupies an important position of the immunology for aging, autoimmune disease, malignancy, bacterial infection, transplantation and allergy (immediate hypersensitivity).