B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.
T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were re-exposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.
Park
Jang-June
JJ
Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, USA.
Omiya
Ryusuke
R
Matsumura
Yumiko
Y
Sakoda
Yukimi
Y
Kuramasu
Atsuo
A
Augustine
Mathew M
MM
Yao
Sheng
S
Tsushima
Fumihiko
F
Narazaki
Hidehiko
H
Anand
Sudarshan
S
Liu
Yingjia
Y
Strome
Scott E
SE
Chen
Lieping
L
Tamada
Koji
K
D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D015153:Blotting, Western; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000502:physiology*; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000943:Antigens, Differentiation; D001324:Autoantigens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010446:Peptide Fragments; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11695-700
16864790
J Immunol. 2003 Feb 1;170(3):1257-66
12538684
J Exp Med. 2006 Apr 17;203(4):883-95
16606670
Arthritis Rheum. 2005 Apr;52(4):1058-62
15818672
Immunity. 2004 Oct;21(4):503-13
15485628
Proc Natl Acad Sci U S A. 1992 May 1;89(9):4210-4
1373896
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13866-71
11698646
Clin Endocrinol (Oxf). 2007 Jul;67(1):125-8
17490403
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10691-6
15249675
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9331-6
18599457
Nature. 2006 Feb 9;439(7077):682-7
16382236
Blood. 2007 Jul 1;110(1):186-92
17392506
Nat Med. 2000 Mar;6(3):283-9
10700230
J Clin Invest. 2006 Apr;116(4):1045-51
16557300
J Immunol. 1999 Nov 1;163(9):4819-25
10528182
J Clin Invest. 2003 Feb;111(3):363-70
12569162
Tissue Antigens. 2003 Dec;62(6):492-7
14617032
Blood. 2005 Jul 1;106(1):201-6
15774618
Trends Immunol. 2006 Apr;27(4):195-201
16500147
J Immunol. 2004 Mar 1;172(5):2778-84
14978077
J Immunol. 2005 Mar 15;174(6):3377-85
15749870
J Biol Chem. 2002 Mar 8;277(10):7766-75
11726649
Nat Rev Immunol. 2004 May;4(5):336-47
15122199
Mol Biotechnol. 2002 Jul;21(3):259-64
12102550
J Immunol. 2009 Feb 15;182(4):2102-12
19201863
J Immunol. 2004 Jan 1;172(1):34-9
14688306
J Immunol. 2000 Mar 1;164(5):2515-22
10679089
Blood. 2008 Apr 1;111(7):3635-43
18223165
Immunol Rev. 2005 Aug;206:232-59
16048553
Int Immunol. 1998 Apr;10(4):491-8
9620605
Immunity. 2007 Jul;27(1):111-22
17629517
Blood. 2004 Jan 1;103(1):177-84
12969968
J Immunol. 2006 Mar 15;176(6):3480-9
16517716
Nat Genet. 2002 Dec;32(4):666-9
12402038
Nat Med. 2002 Aug;8(8):793-800
12091876
Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10398-403
15235129
Eur J Immunol. 2002 Oct;32(10):2997-3006
12355454
Mol Cell Biol. 2005 Nov;25(21):9543-53
16227604
Nat Immunol. 2005 Mar;6(3):280-6
15685176
J Immunol. 2004 Jul 15;173(2):945-54
15240681
Blood. 2007 Jul 1;110(1):180-5
17289811
Immunity. 2008 Sep 19;29(3):464-75
18789731
Mol Immunol. 2008 Aug;45(13):3567-72
18585785
J Clin Invest. 2002 Mar;109(5):651-9
11877473
Transplantation. 2007 Mar 27;83(6):774-82
17414712
Cancer Res. 2005 Feb 1;65(3):1089-96
15705911
Immunity. 2004 Mar;20(3):327-36
15030776
J Exp Med. 2009 Dec 21;206(13):3015-29
20008522
Transplantation. 2004 Jan 15;77(1):6-12
14724428
Mucosal Immunol. 2009 Sep;2(5):427-38
19571798
Eur J Immunol. 2008 Oct;38(10):2706-17
18825752