The potent role of graft-derived NKR-P1+TCRalphabeta+ T (NKT) cells in the spontaneous acceptance of rat liver allografts.
BACKGROUND
The mechanism involved in the spontaneous acceptance of liver allografts in some rat strain combinations remains unclear. Immunoregulatory NKR-P1TCRalphabetaT (NKT) cells primarily produce IL-4 and IFN-gamma, and enhance the polarization of immune responses to Th2 and Th1, respectively. The aim of this study was to clarify the role of graft-derived NKT cells in inducing the spontaneous acceptance of rat orthotopic liver transplantation (OLTx)


METHODS
The experimental groups were divided as follows: Group 1, BN to LEW "low responder (acceptor)" combination; Group 2, DA to LEW "high responder (rejector)" combination; naïve BN (Group 3) or LEW recipients (Group 4) with liver allografts from irradiated BN donors. The recipients had liver allografts from irradiated donors reconstituted from the following cell populations 24 hr before harvesting, spleen cells (SPCs, Group 5), IgSPCs (Group 6), IgNKR-P1SPCs (Group 7), and IgTCRabSPCs (Group 8)


RESULTS
In Group 1, the percent of graft-derived NKT cells harvested on day 7 posttransplant were significantly higher than in Group 2. In the case of BN liver allografts that had been irradiated and reconstituted with cell populations including NKT cells (Groups 5 and 6), the mean graft survival (MST) was extended to 39.2+/-5.7 and 38.8+/-8.0 days, respectively. In contrast, when NKT cells were excluded (Groups 7 and 8), the grafts were acutely rejected within MST of 17.8+/-4.0 and 18.8+/-7.7 days, respectively. The concentrations of IL-10 and TGF-beta, but not IL-4 in IgGICs culture supernatants were predominant in the acceptor, whereas those with IFN-gamma predominated in the rejector.


CONCLUSIONS
Graft-derived NKT cells might be responsible for spontaneous acceptance in the rat OLTx.
Kiyomoto
Tetsuma
T
Department of Surgery E1, Osaka University Graduate School of Medicine, Osaka, Japan.
Ito
Toshinori
T
Uchikoshi
Fumihiro
F
Ohkawa
Atsushi
A
Akamaru
Yusuke
Y
Miao
Gang
G
Komoda
Hiroshi
H
Nishida
Toshiro
T
Matsuda
Hikaru
H
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D037181:Lectins, C-Type / Q000032:analysis*; D016031:Liver Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000502:physiology; D014916:Whole-Body Irradiation
D000954:Antigens, Surface; D016207:Cytokines; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta