Activation and self-tolerance of natural killer cells

被引:154
作者
Gasser, Stephan
Raulet, David H.
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA
关键词
DNA damage response; hyporesponsiveness; innate immunity; natural killer cells; tolerance; tumor immunology;
D O I
10.1111/j.1600-065X.2006.00460.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Natural killer (NK) cells are regulated by numerous stimulatory and inhibitory receptors that recognize various classes of cell surface ligands, some of which are expressed by normal healthy cells. We review two key issues in NK cell biology. How do NK cells achieve tolerance to healthy self-cells, despite great potential variability in inhibitory and stimulatory receptor engagement? How is the disease status of unhealthy cells translated into changes in ligand expression and consequent sensitivity to NK cell lysis? Concerning the second question, we review evidence that ligands for one key NK receptor, NKG2D, are induced by the DNA damage response, which is activated in cells exposed to genotoxic stress. Because cancer cells and some infected cells are subject to genotoxic stress, these findings suggest a new concept for how diseased cells are discriminated by the immune system. Second, we review studies that have overturned the prevalent notion that NK cells achieve self-tolerance by expressing inhibitory receptors specific for self-major histocompatibility complex class I molecules. A subset of NK cells lacks such receptors. These NK cells are hyporesponsive when stimulatory receptors are engaged, suggesting that alterations in signaling pathways that dampen stimulatory receptor signals contribute to self-tolerance of NK cells.
引用
收藏
页码:130 / 142
页数:13
相关论文
共 113 条
[1]   Comparative analysis of human NK cell activation induced by NKG2D and natural cytotoxicity receptors [J].
André, P ;
Castriconi, R ;
Espéli, M ;
Anfossi, N ;
Juarez, T ;
Hue, S ;
Conway, H ;
Romagné, F ;
Dondero, A ;
Nanni, M ;
Caillat-Zucman, S ;
Raulet, DH ;
Bottino, C ;
Vivier, E ;
Moretta, A ;
Paul, P .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (04) :961-971
[2]   Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors [J].
Arase, H ;
Mocarski, ES ;
Campbell, AE ;
Hill, AB ;
Lanier, LL .
SCIENCE, 2002, 296 (5571) :1323-1326
[3]   DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis [J].
Bartkova, J ;
Horejsi, Z ;
Koed, K ;
Krämer, A ;
Tort, F ;
Zieger, K ;
Guldberg, P ;
Sehested, M ;
Nesland, JM ;
Lukas, C ;
Orntoft, T ;
Lukas, J ;
Bartek, J .
NATURE, 2005, 434 (7035) :864-870
[4]   Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA [J].
Bauer, Stefan ;
Groh, Veronika ;
Wu, Jun ;
Steinle, Alexander ;
Phillips, Joseph H. ;
Lanier, Lewis L. ;
Spies, Thomas .
JOURNAL OF IMMUNOLOGY, 2018, 200 (07) :2231-2233
[5]   NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway [J].
Billadeau, DD ;
Upshaw, JL ;
Schoon, RA ;
Dick, CJ ;
Leibson, PJ .
NATURE IMMUNOLOGY, 2003, 4 (06) :557-564
[6]   Natural killer cells in antiviral defense: Function and regulation by innate cytokines [J].
Biron, CA ;
Nguyen, KB ;
Pien, GC ;
Cousens, LP ;
Salazar-Mather, TP .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :189-220
[7]   SEVERE HERPESVIRUS INFECTIONS IN AN ADOLESCENT WITHOUT NATURAL-KILLER CELLS [J].
BIRON, CA ;
BYRON, KS ;
SULLIVAN, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (26) :1731-1735
[8]   REJECTION OF CLASS-I MHC-DEFICIENT HEMATOPOIETIC-CELLS BY IRRADIATED MHC-MATCHED MICE [J].
BIX, M ;
LIAO, NS ;
ZIJLSTRA, M ;
LORING, J ;
JAENISCH, R ;
RAULET, D .
NATURE, 1991, 349 (6307) :329-331
[9]   HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C [J].
Braud, VM ;
Allan, DSJ ;
O'Callaghan, CA ;
Söderström, K ;
D'Andrea, A ;
Ogg, GS ;
Lazetic, S ;
Young, NT ;
Bell, JI ;
Phillips, JH ;
Lanier, LL ;
McMichael, AJ .
NATURE, 1998, 391 (6669) :795-799
[10]   Vital involvement of a natural killer cell activation receptor in resistance to viral infection [J].
Brown, MG ;
Dokun, AO ;
Heusel, JW ;
Smith, HRC ;
Beckman, DL ;
Blattenberger, EA ;
Dubbelde, CE ;
Stone, LR ;
Scalzo, AA ;
Yokoyama, WM .
SCIENCE, 2001, 292 (5518) :934-937