Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium.
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.
Capone
Myriam
M
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Lees
Rosemary K
RK
Finke
Daniela
D
Ernst
Bettina
B
Meerwijk
Joost P M Van
JP
MacDonald
H Robson
HR
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D006706:Homeostasis; D039001:Integrin alpha Chains / Q000032:analysis; D053547:Keratin-14; D007633:Keratins / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D016827:CD8 Antigens; D006183:H-2 Antigens; D039001:Integrin alpha Chains; D053547:Keratin-14; C507446:Krt14 protein, mouse; D008024:Ligands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; C091367:alpha E integrins; D001613:beta 2-Microglobulin; D007633:Keratins