COEXPRESSION OF CD8-ALPHA IN CD4(-CELL RECEPTOR ALPHA-BETA(+) T-CELLSMIGRATING INTO THE MURINE SMALL-INTESTINE EPITHELIAL LAYER() T)

We investigated the surface phenotype of CD3(+)CD4(+) T cell receptor (TCR) alpha beta(+) T cells repopulating the intestinal lymphoid tissu es of C.B-17 scid/scid (severe-combined immunodeficient; scid) (H-2(d) , L(d+)) mice. CD4(+) CD8(-) T cells were cell sorter-purified from va rious 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 do nor mice. After transfer of 10(5) cells into young scid mice, a mucosa -homing, memory CD44(hi) CD45RB(lo) CD4+ T cell population was selecti vely engrafted. Large numbers of single-positive (SP) CD3(+) CD2(+) CD 28(+) CD4(+) CD8(-) T cells that expressed the alpha(4) integrin chain CD49d were found in the spleen, the mesenteric lymph nodes, the perit oneal cavity and the gut lamina propria of transplanted scid mice. Une xpectedly, large populations of donor-type double-positive (DP) CD4(+) CD8 alpha(+) CD8 beta(-)T cells with high expression of the CD3/TCR c omplex appeared in the epithelial layer of the small intestine of tran splanted scid mice. In contrast to SP CD4(+) T cells, the intraepithel ial DP T cells showed low expression of the CD2 and the CD28 co-stimul ator molecules, and of the alpha(4) integrin chain CD49d, but expresse d high levels of the alpha(IEL) integrin chain CD103. The TCR-VP reper toire of DP but not SP intraepithelial CD4(+) T cells was biased towar ds 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 inte stine epithelial layer of transplanted scid mice had different abiliti es to repopulate secondary scid recipient mice: SP CD4(+) T cells repo pulated various lymphoid tissues of the immunodeficient host, while in traepithelial 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 ep ithelial layer.