Intestinal CD8αα and CD8αβ Intraepithelial Lymphocytes Are Thymus Derived and Exhibit Subtle Differences in TCRβ Repertoires

Abstract

Intraepithelial lymphocytes (IEL) of the small intestine are anatomically positioned to be in the first line of cellular defense against enteric pathogens. Therefore, determining the origin of these cells has important implications for the mechanisms of T cell maturation and repertoire selection. Recent evidence suggests that murine CD8αα intestinal IELs (iIELs) can mature and undergo selection in the absence of a thymus. We analyzed IEL origin by cell transfer, using two congenic chicken strains. Embryonic day 14 and adult thymocytes did not contain any detectable CD8αα T cells. However, when TCR+ thymocytes were injected into congenic animals, they migrated to the gut and developed into CD8αα iIELs, while TCR− T cell progenitors did not. The TCR Vβ1 repertoire of CD8αα+ TCR Vβ1+ iIELs contained only part of the TCR Vβ1 repertoire of total iIELs, and it exhibited no new members compared with CD8+ T cells in the thymus. This indicated that these T cells emigrated from the thymus at an early stage in their developmental process. In conclusion, we show that while CD8αα iIELs originate in the thymus, T cells acquire the expression of CD8αα homodimers in the gut microenvironment.