Secretion of IFN-gamma but not IL-17 by CD1d-restricted NKT cells enhances rejection of skin grafts expressing epithelial cell-derived antigen.
NKT cells are key regulators of autoimmunity, tumor immune surveillance, and the immune response to pathogens. The role of NKT cells in regulating adaptive immunity to cutaneous Ags is largely unknown. This study explores the role of CD1d-restricted NKT cells in cross-priming of CD8 effector T cells to OVA expressed in epithelial keratinocytes (K5mOVA transgenic mouse). In a skin grafting model, we show that NKT cells enhance the rejection of K5mOVA skin grafts by promoting generation of OVA-specific CD8 effector T cells in the skin-draining lymph nodes. This is associated with a decrease in the proportion of both Th17 cells and IL-17-producing NKT cells within the lymph node, thereby inducing a Th1-biased response by increasing the ratio of IFN-gamma to IL-17 production. Administration of a strong agonist ligand (alpha-galactosylceramide) for NKT cells induced higher levels of local IFN-gamma production, enhancing the rate of K5mOVA graft rejection. Thus, NKT cells can promote adaptive immunity to cell-associated Ag expressed in skin by local regulation of IFN-gamma production in secondary lymphoid tissue during cross-priming of effector CD8 T cells.
Mattarollo
Stephen R
SR
The University of Queensland Diamantina Institute for Cancer, Immunology, and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Yong
Michelle
M
Tan
Lieven
L
Frazer
Ian H
IH
Leggatt
Graham R
GR
D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma; D010047:Ovalbumin
J Immunol. 2006 Aug 1;177(3):1416-20
16849446
Blood. 2008 Feb 15;111(4):2091-100
18003887
J Invest Dermatol. 2009 Jul;129(7):1628-42
19262602
Curr Opin Organ Transplant. 2009 Feb;14(1):23-9
19337142
Int J Mol Med. 2008 Sep;22(3):369-74
18698497
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3330-5
19211791
Nature. 2007 Feb 8;445(7128):648-51
17187052
Nat Immunol. 2009 Jun;10(6):568-70
19448657
J Immunol. 2008 Apr 15;180(8):5167-71
18390697
Cell Immunol. 2008 Jan;251(1):50-5
18423430
Transplantation. 2009 Dec 15;88(11):1261-72
19996925
J Immunol. 2007 Mar 1;178(5):2827-34
17312126
J Clin Invest. 2008 Feb;118(2):597-607
18202747
FEBS Lett. 2006 Oct 9;580(23):5456-66
16962101
Cancer Res. 2009 Mar 1;69(5):2010-7
19244111
J Exp Med. 2000 Sep 4;192(5):741-54
10974039
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11287-92
18685112
J Immunol. 2010 Feb 1;184(3):1242-50
20028654
Cancer Res. 2009 May 15;69(10):4301-8
19401453
Eur J Immunol. 2007 Feb;37(2):406-15
17274003
Eur J Immunol. 2003 Jul;33(7):1879-88
12811848
J Exp Med. 2005 Nov 7;202(9):1279-88
16275765
J Exp Med. 2002 Mar 4;195(5):625-36
11877485
Cell Immunol. 2009;254(2):81-4
19010461
J Natl Cancer Inst. 2004 Nov 3;96(21):1611-9
15523090
J Immunol. 2009 Jul 15;183(2):1463-70
19553527
Blood. 2008 Aug 15;112(4):1308-16
18535199
Curr Opin Allergy Clin Immunol. 2007 Oct;7(5):374-81
17873575
Eur J Immunol. 2008 Oct;38(10):2636-49
18958872
J Clin Invest. 2004 Nov;114(10):1379-88
15545985
Immunol Today. 2000 Nov;21(11):573-83
11094262
Transplantation. 2007 Nov 15;84(9):1071-4
17998858
Virology. 1997 Aug 18;235(1):94-103
9300040
J Immunol. 2009 Aug 1;183(3):2142-9
19587013
J Immunol. 2008 Oct 1;181(7):4733-41
18802076
Arthritis Res Ther. 2009;11(4):R122
19686583
Nature. 2008 Jun 19;453(7198):1051-7
18563156
J Exp Med. 2007 May 14;204(5):995-1001
17470641
J Immunol. 2007 Nov 1;179(9):6228-36
17947698