Selective absence of CD8+ TCRαβ+ intestinal epithelial cells in transgenic mice expressing β2-microglobulin-associated ligands exclusively on thymic cortical epithelium

Abstract

Whereas interactions between the TCRαβ and self MHC:peptide complexes are clearly required for positive selection of mature CD4+ and CD8+ T cells during intrathymic development, the role of self or foreign ligands in maintaining the peripheral T cell repertoire is still controversial. In this report we have utilized keratin 14-β2-microglobulin (K14-β2m)-transgenic mice expressing β2m-associated ligands exclusively on thymic cortical epithelial cells to address the possible influence of TCR:ligand interactions in peripheral CD8+T cell homeostasis. Our data indicate that CD8+ T cells in peripheral lymphoid tissues are present in normal numbers in the absence of self MHC class I:peptide ligands. Surprisingly, however, steady state homeostasis of CD8+ T cells in the intestinal epithelium is severely affected by the absence of β2m-associated ligands. Indeed TCRαβ+ IEL subsets expressing CD8αβ or CD8αα are both dramatically reduced in K14-β2m mice, suggesting that the development, survival or expansion of CD8+ IEL depends upon interaction of the TCR with MHC class I:peptide or other β2m-associated ligands elsewhere than on thymic cortical epithelium. Collectively, our data reveal an unexpected difference in the regulation of CD8+ T cell homeostasis by β2m-associated ligands in the intestine as compared to peripheral lymphoid organs.