Intestinal CD8 alpha alpha and CD8 alpha beta intraepithelial lymphocytes are thymus derived and exhibit subtle differences in TCR beta repertoires

Intraepithelial lymphocytes (IEL) of the small intestine are anatomically p ositioned to be in the first line of cellular defense against enteric patho gens. Therefore, determining the origin of these cells has important implic ations for the mechanisms of T cell maturation and repertoire selection. Re cent evidence suggests that murine CD8 alpha alpha intestinal IELs (iIELs) can mature and undergo selection in the absence of a thymus, We analyzed IE L origin by cell transfer, using two congenic chicken strains. Embryonic da y 14 and adult thymocytes did not contain any detectable CD8 alpha alpha T cells. However, when TCR+ thymocytes were injected into congenic animals, t hey migrated to the gut and developed into CD8 alpha alpha iIELs, while TCR - T cell progenitors did not. The TCR V beta1 repertoire of CD8 alpha alpha (+) TCR V beta1(+) iIELs contained only part of the TCR V beta1 repertoire of total iIELs, and it exhibited no new members compared with CD8(+) T cel ls in the thymus, This indicated that these T cells emigrated from the thym us at an early stage in their developmental process. In conclusion, we show that while CD8 alpha alpha iIELs originate in the thymus, T cells acquire the expression of CD8 alpha alpha homodimers in the gut microenvironment.