Negative Selection of Thymus-Dependent CD4+8+ Intestinal Intraepithelial Lymphocytes by Internal Superantigens

CD4 and CD8 double-positive (DP) T cells were transiently found in the Peyerʹs patch of mice 2 to 3 weeks after birth and preceded the appearance of DP intestinal intraepithelial lymphocytes (iIEL). DP iIEL were detected in euthymic-specific pathogen-free mice, but not in athymic and germ-free mice. The pattern of Vβ genes expressed on these DP iIEL was similar to that of CD4 single-positive peripheral T cells, which reflected the negative selection by internal superantigens. MIs, and I-E, CD8 SPT cells did not receive such a strict negative selection with these antigens. DP iIEL expressed a high density of T cell receptor αβ and CD3 and responded to immobilized anti-CD3 to undergo blastogenesis and de novo IL2 receptor expression. These results indicate that DP iIEIL are mature thymus-dependent T cells immigrated to intraepithelial space via the Peyerʹs patch in response to intestinal antigenic stimulation.