Article: article from journal or magazin.
Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium.
European Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Whereas interactions between the TCRalpha beta 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-beta2-microglobulin (K14-beta2m)-transgenic mice expressing beta2m-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 beta2m-associated ligands. Indeed TCRalpha beta(+) IEL subsets expressing CD8alpha beta or CD8alpha alpha are both dramatically reduced in K14-beta2m mice, suggesting that the development, survival or expansion of CD8(+) IEL depends upon interaction of the TCR with MHC class I:peptide or other beta2m-associated ligands elsewhere than on thymic cortical epithelium. Collectively, our data reveal an unexpected difference in the regulation of CD8(+) T cell homeostasis by beta2m-associated ligands in the intestine as compared to peripheral lymphoid organs.
Animals, Antigens, CD/analysis, Antigens, CD8/analysis, Cell Differentiation, Epithelial Cells/immunology, H-2 Antigens/immunology, Homeostasis, Integrin alpha Chains/analysis, Keratin-14, Keratins/genetics, Keratins/immunology, Ligands, Lymphoid Tissue/cytology, Lymphoid Tissue/immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments/immunology, Peyer's Patches/immunology, Receptors, Antigen, T-Cell, alpha-beta/analysis, Recombinant Fusion Proteins/genetics, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/pathology, Thymus Gland/cytology, Thymus Gland/immunology, beta 2-Microglobulin/genetics, beta 2-Microglobulin/immunology
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