Sequential production of interferon-γ by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of α-galactosylceramide

被引:320
作者
Smyth, MJ
Crowe, NY
Pellicci, DG
Kyparissoudis, K
Kelly, JM
Takeda, K
Yagita, H
Godfrey, DI
机构
[1] Peter MacCallum Canc Inst, Trescowthick Labs, Melbourne, Vic 8006, Australia
[2] Monash Univ Sch Med, Dept Pathol & Immunol, Prahran, Vic, Australia
[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
关键词
D O I
10.1182/blood.V99.4.1259
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The antimetastatic effect of the CD1d-binding glycolipid, a.-galactosylceramide (alpha-GalCer), is mediated by NK1.1(+)T (NKT) cells; however, the mechanisms behind this process are poorly defined. Although it has been shown to involve INK cells and interferon-gamma (IFN-gamma) production, the way these factors collaborate to mediate effective tumor rejection and the importance of other factors characteristic of NKT cell and INK cell activation are unknown. Using gene-targeted mice and antibody treatments, the critical need for interleukin 12 (IL-12),: IFN-gamma, and NK cells has been shown in the antimetastatic activity of alpha-Galcer in the lungs band the liver. By contrast, in lung and liver metastasis models, cytotoxic molecules expressed by INK cells and NKT cells (perforin, Fas ligand, and tumor necrosis factor-related apoptosis-inducing ligand) and an NKT cell-secreted cytokine, IL-4, were not necessary for the antitumor activity of alpha-GalCer. Like IL-12, IL-18 was required for optimal serum IFN-gamma induction and control of lung metastases by alpha-Galcer. IL-18 was unnecessary for alpha-GalCer-related suppression of liver metastases. Most importantly, after adoptive transfer of alpha-GalCer-reactive NKT cells or NK cells into NKT cell-deficient, IFN-gamma-deficient, or RAG-1-deficient mice, it was demonstrated that the sequential production of IFN-gamma by NKT cells and NK cells was absolutely required to reconstitute the antimetastatic activity of alpha-Galcer. (C) 2002 by The American Society of Hematology.
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页码:1259 / 1266
页数:8
相关论文
共 73 条
[1]   FAS-MEDIATED CYTOTOXICITY BY FRESHLY ISOLATED NATURAL-KILLER-CELLS [J].
ARASE, H ;
ARASE, N ;
SAITO, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (03) :1235-1238
[2]   Mouse CD1-specific NK1 T cells: Development, specificity, and function [J].
Bendelac, A ;
Rivera, MN ;
Park, SH ;
Roark, JH .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :535-562
[3]   In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers [J].
Benlagha, K ;
Weiss, A ;
Beavis, A ;
Teyton, L ;
Bendelac, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (11) :1895-1903
[4]   Antigen-presenting function of mouse CD1: one molecule with two different kinds of antigenic ligands [J].
Brossay, L ;
Burdin, N ;
Tangri, S ;
Kronenberg, M .
IMMUNOLOGICAL REVIEWS, 1998, 163 :139-150
[5]  
Brossay L, 1998, J IMMUNOL, V161, P5124
[6]   CD1-mediated immune responses to glycolipids [J].
Burdin, N ;
Kronenberg, M .
CURRENT OPINION IN IMMUNOLOGY, 1999, 11 (03) :326-331
[7]  
Burdin N, 1999, EUR J IMMUNOL, V29, P2014, DOI 10.1002/(SICI)1521-4141(199906)29:06<2014::AID-IMMU2014>3.0.CO
[8]  
2-G
[9]  
Burdin N, 1998, J IMMUNOL, V161, P3271
[10]  
CAMAUD C, 1999, J IMMUNOL, V163, P4647