Hapten application to the skin induces an inflammatory program directing hapten-primed effector CD8 T cell interaction with hapten-presenting endothelial cells.
Contact hypersensitivity is a CD8 T cell-mediated response to hapten sensitization and challenge of the skin. Effector CD8 T cell recruitment into the skin parenchyma to elicit the response to hapten challenge requires prior CXCL1/KC-directed neutrophil infiltration within 3-6 h after challenge and is dependent on IFN-γ and IL-17 produced by the hapten-primed CD8 T cells. Mechanisms directing hapten-primed CD8 T cell localization and activation in the Ag challenge site to induce this early CXCL1 production in response to 2,4-dinitrofluorobenzene were investigated. Both TNF-α and IL-17, but not IFN-γ, mRNA was detectable within 1 h of hapten challenge of sensitized mice and increased thereafter. Expression of ICAM-1 was observed by 1 h after challenge of sensitized and nonsensitized mice and was dependent on TNF-α. The induction of IL-17, IFN-γ, and CXCL1 in the challenge site was not observed when ICAM-1 was absent or neutralized by specific Ab. During the elicitation of the contact hypersensitivity response, endothelial cells expressed ICAM-1 and produced CXCL1 suggesting this as the site of CD8 T cell localization and activation. Endothelial cells isolated from challenged skin of naive and sensitized mice had acquired the hapten and the ability to activate hapten-primed CD8 T cell cytokine production. These results indicate that hapten application to the skin of sensitized animals initiates an inflammatory response promoting hapten-primed CD8 T cell localization to the challenge site through TNF-α-induced ICAM-1 expression and CD8 T cell activation to produce IFN-γ and IL-17 through endothelial cell presentation of hapten.
Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA. kishd@ccf.org
Danielle D
DD
Kish
Nina
N
Volokh
William M
WM
Baldwin
Robert L
RL
Fairchild
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D002450:Cell Communication / Q000276:immunology*; D054360:Chemokine CXCL1 / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology
D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D006241:Haptens; D018836:Inflammation Mediators; D020381:Interleukin-17; D007371:Interferon-gamma
J Immunol. 2003 Jun 1;170(11):5530-7
12759430
Immunity. 2002 Sep;17(3):375-87
12354389
Curr Opin Immunol. 2000 Jun;12(3):336-41
10781407
J Immunol. 1990 Jun 1;144(11):4121-8
1971294
Arthritis Rheum. 2001 Sep;44(9):2176-84
11592383
Lancet. 2001 Jun 9;357(9271):1842-7
11410193
Blood. 2004 Apr 15;103(8):3111-6
15070692
J Allergy Clin Immunol. 2009 Nov;124(5):1022-10.e1-395
19895991
J Exp Med. 2003 Mar 3;197(5):643-56
12615905
N Engl J Med. 1999 May 6;340(18):1398-405
10228190
Annu Rev Cell Biol. 1993;9:317-43
8280464
Cell Death Differ. 2003 Jan;10(1):45-65
12655295
J Immunol. 2000 May 15;164(10):5207-14
10799880
Cardiovasc Res. 2010 May 1;86(2):183-91
20124403
J Immunol. 2001 Sep 15;167(6):3494-504
11544343
Eur J Immunol. 1997 Jan;27(1):111-5
9022006
J Immunol. 2001 Sep 1;167(5):2979-84
11509648
J Leukoc Biol. 1997 Jun;61(6):647-53
9201255
J Exp Med. 1991 Mar 1;173(3):673-9
1900080
J Immunol. 2009 May 15;182(10):5949-59
19414746
Circulation. 2005 Jul 19;112(3):320-31
15998678
Br J Dermatol. 1999 Aug;141(2):192-200
10468787
J Invest Dermatol. 1999 Dec;113(6):888-93
10594726
Cell. 2002 Nov 27;111(5):635-46
12464176
Am J Transplant. 2009 Dec;9(12):2679-96
19788501
Am J Pathol. 1993 Dec;143(6):1724-30
7504889
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14470-5
10588729
Basic Res Cardiol. 2004 Jan;99(1):8-11
14685700
Immunol Lett. 2004 May 15;93(2-3):109-13
15158605
Eur J Immunol. 1995 Nov;25(11):3006-10
7489735
J Exp Med. 1987 Dec 1;166(6):1654-67
3119761
J Immunol. 1997 Dec 15;159(12):6148-55
9550416
Curr Opin Cell Biol. 2008 Oct;20(5):525-32
18499427
J Exp Med. 1996 Mar 1;183(3):1001-12
8642241
Nature. 1999 Aug 19;400(6746):776-80
10466728
N Engl J Med. 1998 Feb 12;338(7):436-45
9459648
J Leukoc Biol. 2005 Apr;77(4):552-9
15629884
J Immunol. 1997 May 15;158(10):4721-8
9144485
J Immunol. 1990 Nov 1;145(9):2833-8
2212665
Am J Pathol. 2001 Dec;159(6):2137-45
11733364
J Immunol. 1999 Apr 15;162(8):4928-37
10202039
J Dermatol. 2005 Jul;32(7):523-33
16335867
J Immunol. 2008 May 15;180(10):6439-46
18453558
J Immunol. 2006 Nov 15;177(10):6852-8
17082599
J Leukoc Biol. 2004 Nov;76(5):941-9
15328335
J Immunol. 2003 Mar 15;170(6):3348-56
12626595
J Clin Invest. 1990 Jun;85(6):1936-43
2161433
J Clin Invest. 2004 Apr;113(8):1158-67
15085195
Kidney Int. 1997 May;51(5):1463-8
9150459
J Immunol. 1998 Apr 1;160(7):3513-21
9531313
Am J Transplant. 2010 Jan;10(1):59-68
19958333
N Engl J Med. 2003 Nov 20;349(21):1987-90
14627782
Eur J Immunol. 1999 Nov;29(11):3485-95
10556803