title: Allergic conjunctivitis exacerbates corneal allograft rejection by activating Th1 and th2 alloimmune responses.
abstract: Allergic conjunctivitis (AC) and airway hyperreactivity exacerbate corneal allograft rejection. Because AC and airway hyperreactivity are allergic diseases of mucosal tissues, we determined whether an allergic disease of a nonmucosal tissue would affect corneal allograft rejection and whether Th2 cells alone accounted for accelerated graft rejection in allergic mice. Hosts sensitized cutaneously with short ragweed pollen developed cutaneous immediate hypersensitivity but rejected corneal allografts at the same tempo and incidence as naive mice. Th2 immune deviation induced with keyhole limpet hemocyanin and IFA did not affect corneal allograft rejection. Thus, Th2 immune deviation alone does not account for the exacerbation of corneal allograft rejection that occurs in mice with AC. CD4(+) T cells from AC mice elaborated Th1 (IFN-gamma) and Th2 (IL-13) cytokines when challenged with donor alloantigens. Adoptive transfer of Th1 or Th2 cells to nude mice, from AC mice that had rejected corneal allografts, produced graft rejection in 70% and 20% of the hosts, respectively. In contrast, adoptive transfer of a combination of Th1 and Th2 cells produced 100% rejection. Administration of exogenous IFN-gamma could substitute for Th1 cells and produced 100% corneal allograft rejection in recipients of Th2 cells alone. By contrast, IFN-gamma did not significantly enhance corneal allograft rejection mediated by Th1 cells. Thus, exacerbation of corneal allograft rejection in mice with AC is associated with a mixed Th1 and Th2 alloimmune response, and the contribution of Th1 cells is through their production of IFN-gamma.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA. jerry.niederkorn@utsouthwestern.edu
authors.forename: Jerry Y
authors.initials: JY
authors.lastname: Niederkorn
authors.forename: Peter W
authors.initials: PW
authors.lastname: Chen
authors.forename: Jessamee
authors.initials: J
authors.lastname: Mellon
authors.forename: Christina
authors.initials: C
authors.lastname: Stevens
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mayhew
mesh_terms: D000818:Animals; D002469:Cell Separation; D003233:Conjunctivitis, Allergic / Q000150:complications / Q000276:immunology*; D016039:Corneal Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
references.citation: Transplantation. 1996 Jul 27;62(2):229-38
references.pmid: 8755821
references.citation: Nat Immunol. 2003 Nov;4(11):1102-10
references.pmid: 14556006
references.citation: Invest Ophthalmol Vis Sci. 1994 Aug;35(9):3505-15
references.pmid: 8056526
references.citation: Clin Immunol Immunopathol. 1998 Apr;87(1):75-84
references.pmid: 9576013
references.citation: Curr Eye Res. 1991 Sep;10(9):889-92
references.pmid: 1790719
references.citation: J Immunol. 2001 Aug 15;167(4):1891-9
references.pmid: 11489968
references.citation: Invest Ophthalmol Vis Sci. 1981 Mar;20(3):355-63
references.pmid: 6782034
references.citation: Immunol Today. 1982 Apr;3(4):97-106
references.pmid: 25291454
references.citation: J Leukoc Biol. 2003 Aug;74(2):167-71
references.pmid: 12885932
references.citation: J Immunol. 2005 Jun 1;174(11):6577-81
references.pmid: 15905494
references.citation: Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2700-7
references.pmid: 8977485
references.citation: J Immunol. 1992 Dec 1;149(11):3468-76
references.pmid: 1358971
references.citation: Br J Ophthalmol. 2000 Aug;84(8):813-5
references.pmid: 10906082
references.citation: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3239-46
references.pmid: 16123425
references.citation: Transplantation. 1991 Feb;51(2):532-6
references.pmid: 1994550
references.citation: Transplantation. 2007 Oct 15;84(7):806-13
references.pmid: 17984831
references.citation: J Clin Invest. 1999 Oct;104(8):1021-9
references.pmid: 10525040
references.citation: J Clin Invest. 1999 Jun;103(12):1659-67
references.pmid: 10377172
references.citation: Nat Immunol. 2003 Jun;4(6):503-5
references.pmid: 12774069
references.citation: Immunology. 2000 Apr;99(4):540-5
references.pmid: 10792501
references.citation: J Immunol. 1993 Mar 1;150(5):1727-34
references.pmid: 8436812
references.citation: Invest Ophthalmol Vis Sci. 1990 Oct;31(10):1950-6
references.pmid: 2210990
references.citation: Am J Transplant. 2009 May;9(5):1017-26
references.pmid: 19422331
references.citation: J Immunol. 2001 Mar 1;166(5):3143-50
references.pmid: 11207266
references.citation: J Immunol. 1996 Sep 1;157(5):1951-7
references.pmid: 8757314
references.citation: Curr Opin Allergy Clin Immunol. 2005 Oct;5(5):446-50
references.pmid: 16131922
references.citation: J Immunol. 1986 Apr 1;136(7):2348-57
references.pmid: 2419430
references.citation: J Immunol. 2009 Jul 1;183(1):155-63
references.pmid: 19535633
references.citation: Transplant Proc. 1997 Feb-Mar;29(1-2):983
references.pmid: 9123616
references.citation: Transplantation. 2005 Jan 15;79(1):23-31
references.pmid: 15714165
references.citation: Invest Ophthalmol Vis Sci. 1997 May;38(6):1130-8
references.pmid: 9152232
references.citation: Nat Immunol. 2004 Mar;5(3):337-43
references.pmid: 14973436
references.citation: Transplantation. 1999 Jun 27;67(12):1503-8
references.pmid: 10401754
references.citation: Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3218-25
references.pmid: 7913917
references.citation: Invest Ophthalmol Vis Sci. 1997 Feb;38(2):292-300
references.pmid: 9040461
references.citation: J Immunol. 1999 May 1;162(9):5247-55
references.pmid: 10227999
references.citation: J Biol Chem. 2002 Jun 7;277(23):20820-4
references.pmid: 11932261
references.citation: J Immunol. 2009 Jan 1;182(1):148-53
references.pmid: 19109145
references.citation: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4044-9
references.pmid: 17724186
references.citation: Clin Exp Immunol. 2001 Oct;126(1):16-28
references.pmid: 11678895
references.citation: J Immunol. 2003 Aug 15;171(4):1637-41
references.pmid: 12902459
references.citation: Nature. 2002 Jan 31;415(6871):536-41
references.pmid: 11823861