Abundance of unconventional CD8(+) natural killer T cells in the large intestine

Natural killer T (NKT) cells are mainly present in the liver and thymus, an d the majority of these T cells express either a CD4(+) or a double-negativ e (DN) CD4(-)8(-) phenotype. In the present study, we examined whether such NKT cells were present in the intestine. NKT cells were rare in all sites of the small intestine, including an intraepithelial site. However, a consi derable number of NKT cells were found at an intraepithelial site in the la rge intestine. This result was confirmed by both immunofluorescence and imm unohistochemistry. In contrast to conventional NKT cells, NKT cells in the large intestine were CD8(+) or DN CD4(-)8(-). In the case of conventional N KT cells, their existence is known to depend on non-classical MHC class I-l ike antigens (i.e. CD1d) but not on classical MHC class I antigens. However , the NKT cells in the large intestine were independent of the presence of both CD1d and classical MHC class I antigens. These results were obtained u sing knockout mice lacking the corresponding genes and molecules. NKT cells in the large intestine were mainly alpha beta TCR+ (> 75%) but did not use an invariant chain of V alpha 14J alpha 281, which is preferentially used by conventional NKT cells. These NKT cells did not bias the TCR-V beta usag e toward V beta8. These findings suggest that the large intestine is a site in which unconventional NKT cells carrying the CD8(+) phenotype (or DN CD4 (-)8(-)) are abundant and that these cells are independent of MHC and MHC-l ike antigens.