Valpha14 NK T cell-triggered IFN-gamma production by Gr-1+CD11b+ cells mediates early graft loss of syngeneic transplanted islets.
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-gamma production triggered by Valpha14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Valpha14 NKT cell-deficient (Jalpha281-/-) mice failed to produce IFN-gamma, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of alpha-galactosylceramide, a specific ligand for Valpha14 NKT cells, resulting in dramatically reduced IFN-gamma production by Gr-1+CD11b+ cells, as well as Valpha14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-gamma they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Valpha14 NKT cell function.
Yasunami
Yohichi
Y
Department of Surgery I, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
Kojo
Satoshi
S
Kitamura
Hiroshi
H
Toyofuku
Atsushi
A
Satoh
Masayuki
M
Nakano
Masahiko
M
Nabeyama
Kentaroh
K
Nakamura
Yoshiichiroh
Y
Matsuoka
Nobuhide
N
Ikeda
Seiyo
S
Tanaka
Masao
M
Ono
Junko
J
Nagata
Naoki
N
Ohara
Osamu
O
Taniguchi
Masaru
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000276:immunology
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D007371:Interferon-gamma