title: Specific destruction of host-reactive mature T cells of donor origin prevents graft-versus-host disease in cyclophosphamide-induced tolerant mice.
abstract: In cyclophosphamide (CP)-induced tolerance, a long lasting skin allograft tolerance was established in many H-2-identical strain combinations without graft vs host disease. Destruction of donor-reactive T cells of host origin, followed by intrathymic clonal deletion of these cells, has been revealed to be the chief mechanisms of this system. Here, we studied the fate of host-reactive populations in donor-derived T cells of C3H/He (C3H) (H-2k, Mls-1b, Mls-2a) mice rendered CP-induced tolerant to AKR/J (AKR) (H-2k, Mls-1a, Mls-2b), by assessing AKR-derived Thy-1.1+ T cells bearing TCR V beta 3 that are specifically reactive with Mls-2a-encoded Ag of the recipient C3H mice. In the AKR-derived Thy-1.1+ lymph node cells of the C3H mice that had been treated with AKR spleen cells plus CP, CD4(+)-V beta 3+ T cells were obviously decreased by day 10 after the CP treatment. At this stage, the Thy-1.1+ T cells were not detected in the C3H thymus, suggesting that the obvious decrease of CD4(+)-V beta 3+ T cells of AKR origin was not due to intrathymic clonal deletion in the recipient C3H mice. Therefore, the destruction of the host-reactive mature T cells of donor origin, as well as that of the donor-reactive mature T cells of host origin, occurred by the CP treatment at the induction phase. Furthermore, after the establishment of intrathymic mixed chimerism in the recipient C3H mice, V beta 3+ T cells were not detected among the Thy-1.1+ T cells of AKR origin in the mixed chimeric thymus, suggesting that the host-reactive immature T cells repopulated from the injected donor hematopoietic cells were clonally deleted in the recipient thymus. These two mechanisms appear to prevent graft vs host disease in CP-induced tolerance.
authors.affiliation: Department of Immunology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Eto
authors.forename: H
authors.initials: H
authors.lastname: Mayumi
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002678:Chimera; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D007519:Isoantigens / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens; D014184:Transplantation, Homologous
chemical_list: D000954:Antigens, Surface; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018800:Thy-1 Antigens; D003520:Cyclophosphamide