Abstract
We investigated the surface phenotype of CD3^+^CD4^+^ T cell receptor (TCR) αβ^+^ T cells repopulating the intestinal lymphoid tissues of C.B‐17 scidlscid (severe‐combined immunodeficient; scid) (H‐2^d^, L^d+^) mice. CD4^+^ CD8^−^ T cells were cell sorter‐purified from various secondary and tertiary lymphoid organs of congenic C.B‐17 +/+ (H‐2^d^, L^d+^) or semi‐syngeneic dm2 (H‐2^d^, L^d−^) immunocompetent donor mice. After transfer of 10^5^ cells into young scid mice, a mucosa‐homing, memory CD44^hi^ CD45RB^lo^ CD4^+^ T cell population was selectively engrafted. Large numbers of single‐positive (SP) CD3^+^ CD2^+^ CD28^+^ CD4^+^ CD^8−^ T cells that expressed the α~4~ integrin chain CD49d were found in the spleen, the mesenteric lymph nodes, the peritoneal cavity and the gut lamina propria of transplanted scid mice. Unexpectedly, large populations of donor‐type doublepositive (DP) CD4^+^ CD8α^+^ CD8β^−^ T cells with high expression of the CD3/TCR complex appeared in the epithelial layer of the small intestine of transplanted scid mice. In contrast to SP CD4^+^ T cells, the intraepithelial DP T cells showed low expression of the CD2 and the CD28 co‐stimulator molecules, and of the α~4~ integrin chain CD49d, but expressed high levels of the α~IEL~ integrin chain CD103. The TCR‐Vβ repertoire of DP but not SP intraepithelial CD4^+^ T cells was biased towards usage of the Vβ6 and Vβ8 viable domains. Highly purified populations of SP and DP CD4^+^ T cell populations from the small intestine epithelial layer of transplanted scid mice had different abilities to repopulate secondary scid recipient mice: SP CD4^+^ T cells repopulated various lymphoid tissues of the immunodeficient host, while intraepithelial DP CD4^+^ T cells did not. Hence, a subset of CD3^+^ CD4^+^ TCRαβ^+^ T cells apparently undergoes striking phenotypic changes when it enters the microenvironment of the small intestine epithelial layer.