Co-expression of CD8 alpha in CD4+ T cell receptor alpha beta + T cells migrating into the murine small intestine epithelial layer.

We investigated the surface phenotype of CD3+CD4+ T cell receptor (TCR) alpha beta + T cells repopulating the intestinal lymphoid tissues of C.B-17 scid/scid (severe-combined immunodeficient; scid) (H-2d, Ld+) mice. CD4+ CD8- T cells were cell sorter-purified from various secondary and tertiary lymphoid organs of congenic C.B-17 +/+ (H-2d, Ld+) or semi-syngeneic dm2 (H-2d, Ld-) immunocompetent donor mice. After transfer of 10(5) cells into young scid mice, a mucosa-homing, memory CD44hi CD45RBlo CD4+ T cell population was selectively engrafted. Large numbers of single-positive (SP) CD3+ CD2+ CD28+ CD4+ CD8- T cells that expressed the alpha 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 double-positive (DP) CD4+ CD8 alpha + CD8 beta - 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 alpha 4 integrin chain CD49d, but expressed high levels of the alpha IEL integrin chain CD103. The TCR-V beta repertoire of DP but not SP intraepithelial CD4+ T cells was biased towards usage of the V beta 6 and V beta 8 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+ TCR alpha beta + T cells apparently undergoes striking phenotypic changes when it enters the microenvironment of the small intestine epithelial layer.