Role of NKT cells in allogeneic islet graft survival.
Although NKT cells expressing CD1d-reactive TCR exerted protective role in autoimmune diseases, the regulatory function of CD1d-dependent NKT cells in alloimmune responses has not been investigated thoroughly. Here, we demonstrated the regulatory effects of NKT cells using a pancreas islet transplantation model. CD40/CD154 blocking induced long-term graft survival in most B6 recipients, but B6.CD1d(-/-) recipients showed co-stimulation blockade-resistant rejection. Adoptive transfer of NKT cells into B6.CD1d(-/-) restored tolerizing capacity of co-stimulatory blockade. Activation of NKT cells was effective for the prolongation of graft survival and up-regulated membrane-bound TGF-beta expression transiently on their cell surface. The activated CD1d-dependent NKT cells inhibited alloantigen-driven cell proliferation through cell contacts and the beneficial effect of CD154 blocking for allograft survival was related to TGF-beta pathway. Thus, we can conclude that NKT cells are essential for the stable allograft survival and the regulatory function is dependent on, at least in part, TGF-beta engagement.
Yang
Seung Hee
SH
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.
Jin
Ji Zhe
JZ
Lee
Se Han
SH
Park
Hyungbae
H
Kim
Chi Hwa
CH
Lee
Dong-Sup
DS
Kim
Suhnggwon
S
Chung
Nam Hyun
NH
Kim
Yon Su
YS
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D006085:Graft Survival / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology; D015854:Up-Regulation
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta