title: Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.
abstract: CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands.
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.affiliation: Department of Internal Medicine, Limoges University Hospital, Limoges, France.
authors.forename: Kim Heang
authors.initials: KH
authors.lastname: Ly
authors.affiliation: INSERM U866, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tournier
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Ciudad
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Gautheron
authors.affiliation: Department of Internal Medicine and Systemic Diseases, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Devilliers
authors.affiliation: Department of Geriatric Internal Medicine, Dijon University Hospital, Dijon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Quipourt
authors.affiliation: Department of Internal Medicine, HP Metz Belle Isle Hospital, Metz, France.
authors.forename: François
authors.initials: F
authors.lastname: Maurier
authors.affiliation: Department of Internal Medicine, Besançon University Hospital, Besançon, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Meaux-Ruault
authors.affiliation: Department of Internal Medicine, Besançon University Hospital, Besançon, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Magy-Bertrand
authors.affiliation: Department of Geriatric Internal Medicine, Dijon University Hospital, Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Manckoundia
authors.affiliation: Department of Rheumatology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France; INSERM 1093, plateforme d'investigation technologique, Dijon University Hospital, 21000 Dijon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Ornetti
authors.affiliation: Department of Rheumatology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Jean-Francis
authors.initials: JF
authors.lastname: Maillefert
authors.affiliation: Department of Internal Medicine and Systemic Diseases, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Besancenot
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.affiliation: Department of Pathology, Limoges University Hospital, Limoges, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Mesturoux
authors.affiliation: Department of Pathology, Limoges University Hospital, Limoges, France.
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
authors.affiliation: Department of Internal Medicine, Limoges University Hospital, Limoges, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fauchais
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.affiliation: Department of Pathology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, François Mitterrand Hospital, Dijon University Hospital, Dijon, France. Electronic address: bernard.bonnotte@u-bourgogne.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000276:immunology / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005260:Female; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D054367:Receptors, CXCR3 / Q000276:immunology / Q000378:metabolism
chemical_list: C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D016207:Cytokines; D005938:Glucocorticoids; D054367:Receptors, CXCR3; D053804:Granzymes; D011241:Prednisone
keywords: Cytotoxic T cells; Giant cell arteritis; Glucocorticoids; T-lymphocyte; Vasculitis