Application of natural killer T-cells to posttransplantation immunotherapy.
Graft-versus-host disease (GVHD) and graft-versus leukemia (GVL) effects are closely related to each other after allogeneic stem cell transplantation. This association exists because of the extensive and complicated interaction between cellular donor components and recipient components concomitant with cytokine storms. It has been demonstrated that part of this interaction may be related to the induction of a variety of regulatory cells, such as regulatory T-cells and natural killer T (NKT) cells. A lower number of NKT cells may be found in patients with autoimmune diseases, cancer, viral infection, and severe GVHD. When activated, NKT cells rapidly release suppressive cytokines, such as interleukin 4 (IL-4), IL-10, and IL-13, as well as inflammatory cytokines, such as interferon gamma and tumor necrosis factor alpha. NKT cells therefore act as a double-edged sword in their progressive or suppressive effects on diseases. Such contradictory phenomena may be related to the function or types of antigen-presenting cells (APCs) in response to their ligand. A single-dose injection of a ligand for NKT cells, alpha-galactosylceramide (alpha-GalCer), can induce immunity through fully mature dendritic cells in an antigen-specific manner. By contrast, multiple injections of alpha-GalCer would induce tolerance, which may be caused by immature APCs. This response suggests that the function of NKT cells can be determined by alpha-GalCer for controlling the immune response. Furthermore, activation of NKT cells followed by activation of APCs and IL-12 production may lead to activation of NK cells and suppress GVHD in mismatched major histocompatibility complex combinations or may induce GVL effects. Control and modification of NKT cell function may play an important role in regulating GVHD/GVL effects.
Fujii
Shin-ichiro
S
Research Unit for Cellular Immunotherapy, Research Center for Allergy and Immunology, Riken, Yokohama, Kanagawa, Japan. fujiis@rcai.riken.jp
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*
Br J Haematol. 2003 Aug;122(4):617-22
12899717
Curr Opin Immunol. 2004 Apr;16(2):157-62
15023407
Blood. 2002 Feb 15;99(4):1259-66
11830474
Blood. 2000 May 1;95(9):2754-9
10779417
J Exp Med. 2003 Dec 1;198(11):1741-52
14657224
J Exp Med. 1999 Apr 5;189(7):1121-8
10190903
Exp Hematol. 2004 Jul;32(7):630-7
15246159
J Exp Med. 2003 Jul 21;198(2):267-79
12874260
J Exp Med. 2000 Sep 4;192(5):755-60
10974040
J Exp Med. 1999 Apr 5;189(7):1073-81
10190898
J Clin Invest. 2000 Jun;105(12):1761-7
10862791
J Immunol. 1996 May 15;156(10):4035-40
8621946
Nature. 2001 Oct 4;413(6855):531-4
11586362
J Immunol. 1999 Nov 15;163(10):5338-45
10553057
J Exp Med. 2003 Jun 16;197(12):1667-76
12796469
Br J Haematol. 2004 May;125(3):400-4
15086423
Blood. 2004 Feb 1;103(3):767-76
12958064
J Exp Med. 1998 Jun 15;187(12):2109-14
9625772
Int J Hematol. 2003 Jul;78(1):7-17
12894845
J Exp Med. 2002 Aug 5;196(3):389-99
12163567
Curr Opin Immunol. 2003 Dec;15(6):683-9
14630203
J Immunol. 2003 Nov 15;171(10):5140-7
14607913
J Exp Med. 2003 Apr 7;197(7):919-25
12682111
J Exp Med. 1987 Nov 1;166(5):1280-9
3316469
J Immunol. 1992 Jan 15;148(2):373-80
1309556
Science. 2002 Mar 15;295(5562):2097-100
11896281
J Immunol. 2001 Mar 15;166(6):4209-15
11238673
Int J Hematol. 2001 Jul;74(1):26-32
11530801
Eur J Immunol. 2002 Sep;32(9):2551-61
12207339
Nat Immunol. 2002 Sep;3(9):867-74
12154358
J Exp Med. 1998 Apr 6;187(7):1047-56
9529321
J Immunol. 2002 Nov 15;169(10):5564-70
12421933
Nat Med. 1997 Apr;3(4):409-13
9095174
J Immunol. 2004 Feb 1;172(3):1333-9
14734707
Curr Opin Hematol. 2001 Nov;8(6):355-9
11604575
J Exp Med. 2004 Jun 21;199(12):1607-18
15197224
Nat Rev Immunol. 2002 Dec;2(12):957-64
12461568
Eur J Immunol. 2000 Apr;30(4):985-92
10760785
J Immunol Methods. 2003 Jan 15;272(1-2):147-59
12505720
Bone Marrow Transplant. 2004 Oct;34(7):595-602
15300228
Nat Med. 2001 Sep;7(9):1052-6
11533710
Blood. 2002 Sep 1;100(5):1728-33
12176894
J Immunol. 1990 Nov 15;145(10):3209-15
1977798
Nat Immunol. 2002 Jan;3(1):6-8
11753399
Blood. 1998 Jun 1;91(11):4051-5
9596649
Nat Med. 2002 Jun;8(6):575-81
12042807
J Immunol. 1985 Nov;135(5):3004-10
3876371
Nat Immunol. 2000 Dec;1(6):515-20
11101874
J Immunol. 2001 Aug 15;167(4):2087-96
11489992
Blood. 2001 May 15;97(10):2923-31
11342413