Role of NKT cells in allogeneic islet graft survival

Clin Immunol. 2007 Sep;124(3):258-66. doi: 10.1016/j.clim.2007.06.003. Epub 2007 Jul 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism*
  • Antigens, CD1d
  • Graft Survival / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Islets of Langerhans Transplantation / immunology*
  • Killer Cells, Natural / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Transplantation Tolerance / immunology
  • Up-Regulation

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • Histocompatibility Antigens Class II
  • Transforming Growth Factor beta