Characterization of extrathymic CD8 alpha beta T cells in the liver and intestine in TAP-1 deficient mice.
TAP-1 deficient (-/-) mice cannot transport MHC class I antigens onto the cell surface, which results in failure of the generation of CD8+ T cells in the thymus. In a series of recent studies, it has been proposed that extrathymic T cells are generated in the liver and at other extrathymic sites (e.g. the intestine). It was therefore investigated whether CD8+ extrathymic T cells require an interaction with MHC class I antigens for their differentiation in TAP-1(-/-) mice. Although CD8+ thymically derived T cells were confirmed to be absent in the spleen as well as in the thymus, CD8 alpha beta+ T cells were abundant in the livers and intestines of TAP-1(-/-) mice. These CD8+ T cells expanded in the liver as a function of age and were mainly confined to a NK1.1-CD3int population which is known to be truly of extrathymic origin. Hepatic lymphocytes, which contained CD8+ T cells and which were isolated from TAP-1(-/-) mice (H-2b), responded to neither mutated MHC class I antigens (bm1) nor allogeneic MHC class I antigens (H-2d) in in vitro mixed lymphocyte cultures. However, the results from repeated in vivo stimulations with alloantigens (H-2d) were interesting. Allogeneic cytotoxicity was induced in liver lymphocytes in TAP-1(-/-) mice, although the magnitude of cytotoxicity was lower than that of liver lymphocytes in immunized B6 mice. All allogeneic cytotoxicity disappeared with the elimination of CD8+ cells in TAP-1(-/-) mice. These results suggest that the generation and function of CD8+ extrathymic T cells are independent of the existence of the MHC class I antigens of the mouse but have a limited allorecognition ability.
Tsukada
Chika
C
Department of Immunology, Niigata University School of Medicine, Niigata, Japan.
Miyaji
Chikako
C
Kawamura
Hiroki
H
Miyakawa
Ryoko
R
Yokoyama
Hisashi
H
Ishimoto
Yuiko
Y
Miyazawa
Shinobu
S
Watanabe
Hisami
H
Abo
Toru
T
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000375:Aging / Q000276:immunology; D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008099:Liver / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse