title: Development of CD8 alpha alpha+ intestinal intraepithelial T cells in beta 2-microglobulin- and/or TAP1-deficient mice.
abstract: The development of CD8+ intestinal intraepithelial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules, owing to either a mutated beta 2-microglobulin (beta 2m) gene or a mutated transporter associated with Ag processing 1 (TAP1) gene, and in mice doubly homozygous for beta 2m and TAPI mutations. In all mutant mice, the population size of major CD8 alpha alpha+ and CD8 alpha beta+ alpha beta-IEL subsets was reduced drastically, and this resulted in a conspicuous decrease in the total number of alpha beta-IEL. Concomitantly, a compensatory two- to threefold increase in the number of gamma delta-IEL consisting mostly of CD8 alpha alpha+ subset was noted. In radiation bone marrow chimeras, this wild-type/mutant phenotype was determined by the genotype of radioresistant host cells, but was not determined by the genotype of reconstituting bone marrow-derived cells. In beta 2m X TCR-delta double mutant mice, however, the CD8 alpha alpha+ but not CD8 alpha beta+ alpha beta-IEL subset expanded dramatically. Thus, in the absence of gamma delta-IEL, alpha beta-IEL in beta 2m-deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8 alpha alpha+ lymphocyte population of alpha beta- and gamma delta-IEL is not dependent, but that of CD8 alpha beta+ lymphocyte population of alpha beta-IEL is dependent on beta 2m- and/or TAP1-dependent MHC class I molecules, expressed by the controlling cells present in the anatomical site, where the development of IEL takes place.
authors.affiliation: Department of Microbiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiura
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Obana
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Nanno
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics* / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000528:radiation effects; D002454:Cell Differentiation / Q000276:immunology; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000528:radiation effects; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin