OX40 induces CCL20 expression in the context of antigen stimulation: an expanding role of co-stimulatory molecules in chemotaxis.
OX40 is an inducible co-stimulatory molecule expressed by activated T cells. It plays an important role in the activation and proliferation of T lymphocytes. Recently, some co-stimulatory molecules have been shown to direct leukocyte trafficking. Chemotaxis is essential for achieving an effective immune response. CCL20 is an important chemoattractant produced by activated T cells. In this study, using DO11.10 mice whose transgenic T cell receptor specifically recognizes ovalbumin, we demonstrate that ovalbumin induces OX40 expression in CD4+ lymphocytes. Further stimulation of OX40 by OX40 activating antibody up-regulates CCL20 production. Both NF-kappaB dependent and independent signaling pathways are implicated in the induction of CCL20 by OX40. Finally, we primed the DO11.10 splenocytes with or without OX40 activating antibody in the presence of ovalbumin. Intranasal administration of the cell lysates derived from the cells with OX40 stimulation results in more severe leukocyte infiltration in the lung of DO11.10 mice, which is substantially attenuated by CCL20 blocking antibody. Taken together, this study has shown that activation of OX40 induces CCL20 expression in the presence of antigen stimulation. Thus, our results broaden the role of OX40 in chemotaxis, and reveal a novel effect of co-stimulatory molecules in orchestrating both T cell up-regulation and migration.
Zhong
Wenwei
W
Department of Pediatrics, RuiJin Hospital, Shanghai 200025, China.
Zhang
Zili
Z
Hinrichs
David
D
Wu
Xiumei
X
Hall
Mark
M
Xia
Zhenwei
Z
Rosenbaum
James T
JT
D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002457:Cell Extracts; D054418:Chemokine CCL20 / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D019570:Inhalation Exposure; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009500:Neutralization Tests; D010047:Ovalbumin / Q000276:immunology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D053262:Receptors, OX40 / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D000941:Antigens; D002457:Cell Extracts; D054418:Chemokine CCL20; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D053262:Receptors, OX40; D010047:Ovalbumin; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
J Exp Med. 2000 Jan 17;191(2):201-6
10637265
Clin Diagn Lab Immunol. 2002 Mar;9(2):320-3
11874870
J Exp Med. 2003 Jul 21;198(2):315-24
12860930
J Immunol. 2005 Nov 15;175(10):6676-85
16272323
Immunol Rev. 2009 Mar;228(1):253-72
19290933
J Exp Med. 2007 Nov 26;204(12):2803-12
18025126
Cytokine. 2009 Apr;46(1):79-91
19254849
Blood. 2007 Apr 1;109(7):2968-77
17119120
Nat Immunol. 2001 Mar;2(3):203-9
11224518
J Exp Med. 1998 Jul 20;188(2):297-304
9670042
Cytokine Growth Factor Rev. 2003 Oct;14(5):409-26
12948524
J Biol Chem. 1997 Aug 1;272(31):19518-24
9235955
J Immunol. 2008 Dec 15;181(12):8391-401
19050256
Nat Rev Immunol. 2009 Apr;9(4):271-85
19319144
Immunol Rev. 2009 May;229(1):173-91
19426222
Nat Immunol. 2007 Sep;8(9):950-7
17676044
Immunol Rev. 2009 May;229(1):337-55
19426232
Nat Immunol. 2001 Jun;2(6):487-92
11376334
J Immunol. 2000 Oct 15;165(8):4470-7
11035086
FEBS Lett. 1998 Nov 27;440(1-2):188-94
9862452
Biochem Soc Trans. 2007 Nov;35(Pt 5):1114-8
17956291
Eur J Immunol. 2009 Apr;39(4):996-1006
19350575
J Leukoc Biol. 2008 Mar;83(3):648-62
18089854
J Pathol. 2008 Jan;214(2):179-89
18161751
J Allergy Clin Immunol. 2009 May;123(5):1004-11
19410689
Exp Eye Res. 2009 Oct;89(4):522-31
19524567
Immunol Res. 2008;42(1-3):41-50
18629448
J Leukoc Biol. 2001 Sep;70(3):439-46
11527994
J Immunol. 1999 Jan 15;162(2):1077-83
9916736
Biochem J. 2009 Feb 15;418(1):13-27
19159344
J Immunol. 2002 Jun 1;168(11):5621-8
12023359
Nat Rev Immunol. 2003 Apr;3(4):317-30
12669022
Ciba Found Symp. 1997;204:148-54; discussion 154-8
9107418
Biochim Biophys Acta. 2009 May;1789(5):386-94
19303953
Nat Rev Immunol. 2001 Dec;1(3):220-8
11905831
Nat Immunol. 2009 Oct;10(10):1125-32
19734905
Trends Immunol. 2007 Jun;28(6):267-73
17481953
Immunol Rev. 2008 Jun;223:87-113
18613831
J Immunol. 1997 Feb 1;158(3):1033-6
9013939
Eur J Immunol. 1999 Feb;29(2):633-42
10064080
Arthritis Res Ther. 2008;10 Suppl 1:S3
19007423
Infect Immun. 1997 Mar;65(3):865-71
9038289
Immunol Rev. 2008 Dec;226:147-59
19161422
Curr Biol. 2000 Mar 23;10(6):R227-30
10744968
Infect Immun. 2001 Apr;69(4):2736-8
11254644
Vaccine. 2006 Feb 13;24(7):872-83
16176850
J Immunol. 1999 Feb 1;162(3):1818-26
9973447