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  • Title: Role of gut cryptopatches in early extrathymic maturation of intestinal intraepithelial T cells.
    Author: Oida T, Suzuki K, Nanno M, Kanamori Y, Saito H, Kubota E, Kato S, Itoh M, Kaminogawa S, Ishikawa H.
    Journal: J Immunol; 2000 Apr 01; 164(7):3616-26. PubMed ID: 10725718.
    Abstract:
    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 (CRgamma-/Y) in which CP were undetectable. IEL-expressing TCR-gammadelta (gammadelta-IEL) were absent, and a drastically reduced number of Thy-1highCD4+ and Thy-1highCD8alphabeta+ alphabeta-IEL were present in CRgamma-/Y mice, whereas these alphabeta-IEL disappeared from athymic CRgamma-/Y littermate mice. Athymic CRgamma-/Y mice possessed a small TCR- and alphaEbeta7 integrin-negative IEL population, characterized by the disappearance of the extrathymic CD8alphaalpha+ subset, that expressed pre-Talpha, RAG-2, and TCR-Cbeta but not CD3epsilon transcripts. These TCR- IEL from athymic CRgamma-/Y mice did not undergo Dbeta-Jbeta and Vdelta-Jdelta joinings, despite normal rearrangements at the TCR-beta and -delta loci in thymocytes from euthymic CRgamma-/Y mice. In contrast, athymic severe combined immunodeficient mice in which CP developed normally possessed two major TCR-alphaEbeta7+ CD8alphaalpha+ and CD8- IEL populations that expressed pre-Talpha, RAG-2, TCR-Cbeta, and CD3epsilon transcripts. These findings underscore the role of gut CP in the early extrathymic maturation of CD8alphaalpha+ IEL, including cell-surface expression of alphaEbeta7 integrin, CD3epsilon gene transcription, and TCR gene rearrangements.
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