Vα14 NKT cell-triggered IFN-γ production by Gr-1 +CD11b+ cells mediates early graft loss of syngeneic transplanted islets

Yohichi Yasunami, Satoshi Kojo, Hiroshi Kitamura, Atsushi Toyofuku, Masayuki Satoh, Masahiko Nakano, Kentaroh Nabeyama, Yoshiichiroh Nakamura, Nobuhide Matsuoka, Seiyo Ikeda, Masao Tanaka, Junko Ono, Naoki Nagata, Osamu Ohara, Masaru Taniguchi

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80 Citations (Scopus)

Abstract

Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1 +CD11b+ cells generated by transplantation and their IFN-γ production triggered by Vα14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Vα14 NKT cell-deficient (Jα281-/-) mice failed to produce IFN-γ, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of α-galactosylceramide, a specific ligand for Vα14 NKT cells, resulting in dramatically reduced IFN-γ production by Gr-1+CD11b+ cells, as well as Vα14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1 +CD11b+ cells and the IFN-γ they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Vα14 NKT cell function. JEM

Original languageEnglish
Pages (from-to)913-918
Number of pages6
JournalJournal of Experimental Medicine
Volume202
Issue number7
DOIs
Publication statusPublished - Oct 3 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Yasunami, Y., Kojo, S., Kitamura, H., Toyofuku, A., Satoh, M., Nakano, M., Nabeyama, K., Nakamura, Y., Matsuoka, N., Ikeda, S., Tanaka, M., Ono, J., Nagata, N., Ohara, O., & Taniguchi, M. (2005). Vα14 NKT cell-triggered IFN-γ production by Gr-1 +CD11b+ cells mediates early graft loss of syngeneic transplanted islets. Journal of Experimental Medicine, 202(7), 913-918. https://doi.org/10.1084/jem.20050448