Extrathymic differentiation of intraepithelial lymphocytes: generation of a separate and unequal T-cell repertoire?

A significant number of intraepithelial intestinal T cells appear to mature extrathymically. In this paper, Leo Lefrançois discusses the implication of this for T-cell receptor selection and repertoire generation. He goes on to develop the concept that such cells may constitute discrete subsets of organ-specific lymphocytes, with unique T-cell receptor repertoires that may be evolutionary antecedents of thymus-derived T cells.