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The Journal of Immunology, 2000, 164: 3616-3626.
Copyright © 2000 by The American Association of Immunologists

Role of Gut Cryptopatches in Early Extrathymic Maturation of Intestinal Intraepithelial T Cells1

Takatoku Oida*,{dagger}, Kenji Suzuki*, Masanobu Nanno{ddagger}, Yutaka Kanamori§, Hisashi Saito, Eiro Kubota, Shingo Kato*, Mamoru Itoh||, Shuichi Kaminogawa{dagger} and Hiromichi Ishikawa2,*

* Department of Microbiology, Keio University School of Medicine, Tokyo, Japan; {dagger} Department of Applied Biological Chemistry, University of Tokyo, Tokyo, Japan; {ddagger} Yakult Central Institute for Microbiological Research, Tokyo, Japan; § Department of Pediatric Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan; Second Department of Oral and Maxillofacial Surgery, Kanagawa Dental School, Kanagawa, Japan; and || Central Institute for Experimental Animals, Kanagawa, Japan

Lympho-hemopoietic progenitors residing in murine gut cryptopatches (CP) have been shown to generate intestinal intraepithelial T cells (IEL). To investigate the role of CP in progenitor maturation, we analyzed IEL in male mice with a truncated mutation of common cytokine receptor {gamma}-chain (CR{gamma}-/Y) in which CP were undetectable. IEL-expressing TCR-{gamma}{delta} ({gamma}{delta}-IEL) were absent, and a drastically reduced number of Thy-1highCD4+ and Thy-1highCD8{alpha}ß+ {alpha}ß-IEL were present in CR{gamma}-/Y mice, whereas these {alpha}ß-IEL disappeared from athymic CR{gamma}-/Y littermate mice. Athymic CR{gamma}-/Y mice possessed a small TCR- and {alpha}Eß7 integrin-negative IEL population, characterized by the disappearance of the extrathymic CD8{alpha}{alpha}+ subset, that expressed pre-T{alpha}, RAG-2, and TCR-Cß but not CD3{epsilon} transcripts. These TCR- IEL from athymic CR{gamma}-/Y mice did not undergo Dß-Jß and V{delta}-J{delta} joinings, despite normal rearrangements at the TCR-ß and -{delta} loci in thymocytes from euthymic CR{gamma}-/Y mice. In contrast, athymic severe combined immunodeficient mice in which CP developed normally possessed two major TCR-{alpha}Eß7+ CD8{alpha}{alpha}+ and CD8- IEL populations that expressed pre-T{alpha}, RAG-2, TCR-Cß, and CD3{epsilon} transcripts. These findings underscore the role of gut CP in the early extrathymic maturation of CD8{alpha}{alpha}+ IEL, including cell-surface expression of {alpha}Eß7 integrin, CD3{epsilon} gene transcription, and TCR gene rearrangements.




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