CD4-CD8 lineage differentiation: Thpok-ing into the nucleus.
The mature alphabeta T cell population is divided into two main lineages that are defined by the mutually exclusive expression of CD4 and CD8 surface molecules (coreceptors) and that differ in their MHC restriction and function. CD4 T cells are typically MHC-II restricted and helper (or regulatory), whereas CD8 T cells are typically cytotoxic. Several transcription factors are known to control the emergence of CD4 and CD8 lineages, including the zinc finger proteins Thpok and Gata3, which are required for CD4 lineage differentiation, and the Runx factors Runx1 and Runx3, which contribute to CD8 lineage differentiation. This review summarizes recent advances on the function of these transcription factors in lineage differentiation. We also discuss how the "circuitry" connecting these factors could operate to match the expression of the lineage-committing factors Thpok and Runx3, and therefore lineage differentiation, to MHC specificity.
Wang
Lie
L
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4259, USA.
Bosselut
Rémy
R
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D051379:Mice; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse
Science. 2003 Nov 7;302(5647):1041-3
14605368
Immunity. 2007 Dec;27(6):860-70
18093538
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7384-9
16651517
Science. 2008 Jul 18;321(5887):408-11
18635804
Nat Genet. 2001 Nov;29(3):332-6
11687799
Immunity. 2008 Mar;28(3):297-9
18342002
Nat Immunol. 2004 Jul;5(7):721-9
15195090
Nat Immunol. 2008 Oct;9(10):1131-9
18776905
J Immunol. 2001 Jul 15;167(2):715-23
11441075
Eur J Immunol. 1999 Jun;29(6):1912-8
10382753
Nature. 1989 Oct 26;341(6244):746-9
2571940
Curr Opin Immunol. 2008 Apr;20(2):197-202
18434124
Nat Immunol. 2004 Mar;5(3):280-8
14770180
Mol Cell. 2002 Nov;10(5):1083-96
12453416
Immunity. 2008 Mar;28(3):346-58
18342007
Nature. 2005 Feb 24;433(7028):826-33
15729333
J Exp Med. 2009 Jan 16;206(1):51-9
19139168
Adv Immunol. 2004;83:55-89
15135628
Immunity. 2003 Jul;19(1):83-94
12871641
Nat Immunol. 2006 Apr;7(4):392-400
16491076
J Immunol. 2001 Nov 1;167(9):4957-65
11673502
Nat Immunol. 2007 Jul;8(7):687-94
17579647
J Immunol. 2005 Aug 1;175(3):1694-705
16034110
J Exp Med. 2008 Jan 21;205(1):245-56
18195075
Annu Rev Immunol. 2007;25:297-336
17150027
Nat Rev Immunol. 2008 Oct;8(10):788-801
18802443
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7731-6
12796513
Curr Opin Immunol. 2005 Apr;17(2):116-21
15766669
Nat Immunol. 2005 Apr;6(4):373-81
15750595
Nature. 1988 Sep 15;335(6187):229-33
2970593
Immunity. 2005 Mar;22(3):317-28
15780989
EMBO J. 2007 Aug 8;26(15):3629-40
17641686
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8187-92
9653162
J Exp Med. 2007 Aug 6;204(8):1945-57
17646406
Immunol Lett. 2007 Jan 15;108(1):1-9
17084908
Immunity. 2008 Oct 17;29(4):523-37
18957265
Curr Opin Immunol. 2006 Apr;18(2):135-42
16480861
Nat Rev Immunol. 2009 Feb;9(2):125-35
19151747
EMBO J. 1994 Aug 1;13(15):3570-9
8062832
Nature. 1988 Sep 15;335(6187):271-4
3261843
Cell. 1994 Jun 17;77(6):917-29
8004678
Nat Rev Immunol. 2009 Feb;9(2):106-15
19165227
Curr Opin Genet Dev. 2000 Aug;10(4):370-9
10889068
Nat Immunol. 2007 Feb;8(2):145-53
17195845
Science. 1999 Nov 5;286(5442):1149-53
10550051
Eur J Immunol. 2007 Apr;37(4):1043-52
17357106
J Exp Med. 2007 Aug 6;204(8):1749-55
17646405
J Immunol. 2004 Apr 1;172(7):4359-70
15034051
J Immunol. 2005 Mar 1;174(5):2627-36
15728469
Nat Immunol. 2008 Oct;9(10):1122-30
18776904
Annu Rev Immunol. 2003;21:139-76
12414722
J Exp Med. 2003 Jul 7;198(1):51-61
12835475
Nat Rev Immunol. 2002 May;2(5):309-22
12033737
Nat Immunol. 2008 Oct;9(10):1113-21
18776907
Science. 2008 Feb 8;319(5864):822-5
18258917
Immunity. 2000 Jul;13(1):59-71
10933395
Blood. 2004 Apr 1;103(7):2522-9
14630789
Curr Opin Immunol. 2002 Apr;14(2):207-15
11869894
Immunity. 2005 Jul;23(1):75-87
16039581
Immunol Rev. 1998 Oct;165:149-66
9850859
Nat Rev Cancer. 2002 Jul;2(7):502-13
12094236
Immunity. 2003 Dec;19(6):863-75
14670303
Immunity. 2008 Dec 19;29(6):876-87
19062319
J Immunol. 2007 Oct 1;179(7):4405-14
17878336
J Immunol. 2006 Nov 15;177(10):6650-9
17082577
J Exp Med. 2007 Sep 3;204(9):2115-29
17698590
Cell. 2002 Nov 27;111(5):621-33
12464175
Nat Immunol. 2004 Nov;5(11):1157-65
15475959
Curr Opin Cell Biol. 2002 Apr;14(2):140-8
11891111
J Exp Med. 2007 Feb 19;204(2):267-72
17296789
Cell Mol Immunol. 2007 Feb;4(1):15-29
17349208