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The Journal of Immunology, 2000, 165: 6716-6722.
Copyright © 2000 by The American Association of Immunologists

Intestinal CD8{alpha}{alpha} and CD8{alpha}ß Intraepithelial Lymphocytes Are Thymus Derived and Exhibit Subtle Differences in TCRß Repertoires1

Beat A. Imhof2,*, Dominique Dunon2,{dagger}, David Courtois{dagger}, Marko Luhtala{ddagger} and Olli Vainio{ddagger}

* Department of Pathology, Geneva University, Geneva, Switzerland; {dagger} Unité Mixte de Recherche 7622, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, Paris, France; and {ddagger} Department of Medical Microbiology, Turku University, Turku, Finland

Intraepithelial lymphocytes (IEL) of the small intestine are anatomically positioned to be in the first line of cellular defense against enteric pathogens. Therefore, determining the origin of these cells has important implications for the mechanisms of T cell maturation and repertoire selection. Recent evidence suggests that murine CD8{alpha}{alpha} intestinal IELs (iIELs) can mature and undergo selection in the absence of a thymus. We analyzed IEL origin by cell transfer, using two congenic chicken strains. Embryonic day 14 and adult thymocytes did not contain any detectable CD8{alpha}{alpha} T cells. However, when TCR+ thymocytes were injected into congenic animals, they migrated to the gut and developed into CD8{alpha}{alpha} iIELs, while TCR- T cell progenitors did not. The TCR Vß1 repertoire of CD8{alpha}{alpha}+ TCR Vß1+ iIELs contained only part of the TCR Vß1 repertoire of total iIELs, and it exhibited no new members compared with CD8+ T cells in the thymus. This indicated that these T cells emigrated from the thymus at an early stage in their developmental process. In conclusion, we show that while CD8{alpha}{alpha} iIELs originate in the thymus, T cells acquire the expression of CD8{alpha}{alpha} homodimers in the gut microenvironment.




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