Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment.
Some mature natural killer (NK) cells cannot be inhibited by major histocompatibility complex (MHC) I molecules, either because they lack corresponding inhibitory receptors or because the host lacks the corresponding MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant and exhibit a generalized hyporesponsiveness to stimulation through activating receptors. To address whether NK cell responsiveness is set only during the NK cell differentiation process, we transferred mature NK cells from wild-type (WT) to MHC I-deficient hosts or vice versa. Remarkably, mature responsive NK cells from WT mice became hyporesponsive after transfer to MHC I-deficient mice, whereas mature hyporesponsive NK cells from MHC I-deficient mice became responsive after transfer to WT mice. Altered responsiveness was evident among mature NK cells that had not divided in the recipient animals, indicating that the cells were mature before transfer and that alterations in activity did not require cell division. Furthermore, the percentages of NK cells expressing KLRG1, CD11b, CD27, and Ly49 receptors specific for H-2(b) were not markedly altered after transfer. Thus, the functional activity of mature NK cells can be reset when the cells are exposed to a changed MHC environment. These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease.
Joncker
Nathalie T
NT
Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
Shifrin
Nataliya
N
Delebecque
Frédéric
F
Raulet
David H
DH
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology
D039481:CD11b Antigen; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
Int J Cancer. 1975 Aug 15;16(2):230-9
1080480
Nat Rev Immunol. 2006 Jul;6(7):520-31
16799471
Immunity. 2002 Jul;17(1):19-29
12150888
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2731-6
10694580
Blood. 2009 Mar 12;113(11):2434-41
18974374
Blood. 2007 Jun 1;109(11):4816-24
17341666
Nature. 1991 Jan 24;349(6307):329-31
1987491
J Immunol. 2009 Apr 15;182(8):4572-80
19342631
J Immunol. 1997 Feb 15;158(4):1628-33
9029098
J Immunol. 2008 Dec 1;181(11):7453-7
19017932
Immunity. 2009 Oct 16;31(4):654-64
19818653
J Exp Med. 1994 Feb 1;179(2):661-72
8294874
J Immunol. 2006 Feb 1;176(3):1517-24
16424180
Blood. 2005 Jun 1;105(11):4416-23
15728129
Annu Rev Immunol. 1999;17:189-220
10358757
Eur J Immunol. 2010 Mar;40(3):813-23
20039300
Eur J Immunol. 2000 Mar;30(3):920-30
10741410
Immunol Rev. 2002 Oct;188:9-21
12445277
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8102-7
15141080
J Immunol. 2007 Nov 1;179(9):5977-89
17947671
Nature. 1989 Nov 23;342(6248):435-8
2685607
Annu Rev Immunol. 2005;23:225-74
15771571
Blood. 2002 May 15;99(10):3661-7
11986221
Immunol Rev. 1997 Feb;155:41-52
9059881
Eur J Immunol. 1975 Feb;5(2):117-21
1086218
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12879-84
19561305
Int Immunol. 1997 Apr;9(4):533-40
9138013
Immunol Rev. 2008 Aug;224:85-97
18759922
Nat Immunol. 2010 Apr;11(4):321-7
20190757
Annu Rev Immunol. 2001;19:197-223
11244035
Mol Med. 2009 Sep-Oct;15(9-10):352-8
19603102
Blood. 2009 May 28;113(22):5488-96
19234143
Nat Immunol. 2002 Jun;3(6):523-8
12006976
Immunity. 2009 Mar 20;30(3):337-47
19249231