title: CD8⁺ cells regulate the T helper-17 response in an experimental murine model of Sjögren syndrome.
abstract: This study investigated the regulatory function of CD8⁺ cells in T helper-17 (Th17) cell-mediated corneal epithelial barrier disruption that develops in a murine desiccating stress (DS) model that resembles Sjögren syndrome. CD8⁺ cell depletion promoted generation of interleukin-17A (IL-17A)-producing CD4⁺ T cells via activation of dendritic cells in both the ocular surface and draining cervical lymph nodes in C57BL/6 mice subjected to DS. T-cell-deficient nude recipient mice receiving adoptively transferred CD4⁺ T cells from CD8⁺ cell-depleted donors exposed to DS displayed increased CD4⁺ T-cell infiltration and elevated IL-17A and CC-chemokine attractant ligand 20 levels in the ocular surface, which was associated with greater corneal barrier disruption. Enhanced DS-specific corneal barrier disruption in CD8-depleted donor mice correlated with a Th17-mediated expression of matrix metalloproteinases (MMP-3 and MMP-9) in the recipient corneal epithelium. Co-transfer of CD8⁺CD103⁺ regulatory T cells did not affect the ability of DS-specific pathogenic CD4⁺ T cells to infiltrate and cause ocular surface disease in the nude recipients, showing that CD8⁺ cells regulate the efferent arm of DS-induced immune response. In summary, CD8⁺ regulatory cells suppress generation of a pathogenic Th17 response that has a pivotal role in DS-induced disruption of corneal barrier function.
authors.affiliation: 1] Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA [2] Department of Ophthalmology, Shenyang He Eye Hospital, Shenyang, Liaoning Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Allergan, Irvine, California, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Schaumburg
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Coursey
authors.affiliation: Department of Biological Sciences, Allergan, Irvine, California, USA.
authors.forename: K F
authors.initials: KF
authors.lastname: Siemasko
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Volpe
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Gandhi
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: D-Q
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Niederkorn
authors.affiliation: 1] Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA [2] Department of Biological Sciences, Allergan, Irvine, California, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Stern
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, and the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: de Paiva
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003315:Cornea / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D012859:Sjogren's Syndrome / Q000276:immunology*; D013312:Stress, Physiological; D058504:Th17 Cells / Q000276:immunology*
references.citation: J Immunol. 2000 Jun 15;164(12):6621-32
references.pmid: 10843722
references.citation: Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3356-65
references.pmid: 17921324
references.citation: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4293-301
references.pmid: 15557435
references.citation: Cell Mol Immunol. 2005 Feb;2(1):11-9
references.pmid: 16212906
references.citation: Int Immunopharmacol. 2009 May;9(5):546-8
references.pmid: 19539566
references.citation: Ophthalmology. 1986 Oct;93(10):1276-83
references.pmid: 2947025
references.citation: J Immunol. 2008 Feb 15;180(4):2573-80
references.pmid: 18250468
references.citation: Histopathology. 1988 Aug;13(2):191-202
references.pmid: 3169687
references.citation: Hum Immunol. 2008 Nov;69(11):781-9
references.pmid: 18812196
references.citation: J Exp Med. 2004 Nov 1;200(9):1123-34
references.pmid: 15520244
references.citation: J Immunol. 2011 Jan 1;186(1):41-52
references.pmid: 21098236
references.citation: Rheumatology (Oxford). 2010 Feb;49(2):246-58
references.pmid: 20007286
references.citation: J Immunol. 2006 Apr 1;176(7):3950-7
references.pmid: 16547229
references.citation: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3293-302
references.pmid: 16877394
references.citation: Hum Immunol. 2008 Nov;69(11):737-44
references.pmid: 18822329
references.citation: Am J Respir Cell Mol Biol. 2002 Jun;26(6):748-53
references.pmid: 12034575
references.citation: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2553-60
references.pmid: 17525184
references.citation: PLoS One. 2011;6(12):e29017
references.pmid: 22194977
references.citation: J Immunol. 1999 Jun 1;162(11):6641-9
references.pmid: 10352281
references.citation: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):826-31
references.pmid: 10711700
references.citation: Nat Rev Immunol. 2004 Nov;4(11):841-55
references.pmid: 15516964
references.citation: J Autoimmun. 2008 Nov;31(3):252-6
references.pmid: 18502610
references.citation: Exp Eye Res. 2005 Sep;81(3):313-25
references.pmid: 16129099
references.citation: J Immunol. 2006 Sep 1;177(5):2775-83
references.pmid: 16920912
references.citation: Nat Immunol. 2007 Apr;8(4):345-50
references.pmid: 17375096
references.citation: J Immunol. 2004 Jan 1;172(1):214-21
references.pmid: 14688328
references.citation: J Exp Med. 2006 Oct 2;203(10):2271-9
references.pmid: 16982811
references.citation: J Gastroenterol. 2007 Sep;42(9):746-53
references.pmid: 17876544
references.citation: Metab Brain Dis. 2011 Jun;26(2):107-13
references.pmid: 21437674
references.citation: Mucosal Immunol. 2009 May;2(3):243-53
references.pmid: 19242409
references.citation: J Immunol. 2008 Jun 1;180(11):7414-22
references.pmid: 18490741
references.citation: Expert Opin Biol Ther. 2009 Aug;9(8):951-65
references.pmid: 19522557
references.citation: Nat Med. 2004 Aug;10(8):801-5
references.pmid: 15286781
references.citation: Autoimmun Rev. 2010 Jun;9(8):560-8
references.pmid: 20385256
references.citation: Am J Pathol. 2005 Jan;166(1):61-71
references.pmid: 15632000
references.citation: Exp Eye Res. 2006 Sep;83(3):526-35
references.pmid: 16643899
references.citation: PLoS One. 2012;7(5):e36822
references.pmid: 22590618