Role of gut cryptopatches in early extrathymic maturation of intestinal intraepithelial T cells.
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.
Oida
T
T
Department of Microbiology, Keio University School of Medicine, Tokyo, Japan.
Suzuki
K
K
Nanno
M
M
Kanamori
Y
Y
Saito
H
H
Kubota
E
E
Kato
S
S
Itoh
M
M
Kaminogawa
S
S
Ishikawa
H
H
D000818:Animals; D017252:CD3 Complex / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D016023:Integrins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D017252:CD3 Complex; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D016023:Integrins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018121:Receptors, Cytokine; D018800:Thy-1 Antigens; C064655:V(D)J recombination activating protein 2; C070709:integrin alphaEbeta7