Involvement and prognosis value of CD8(+) T cells in giant cell arteritis

J Autoimmun. 2016 Aug:72:73-83. doi: 10.1016/j.jaut.2016.05.008. Epub 2016 May 25.

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.

Keywords: Cytotoxic T cells; Giant cell arteritis; Glucocorticoids; T-lymphocyte; Vasculitis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL11 / immunology
  • Chemokine CXCL11 / metabolism
  • Chemokine CXCL9 / immunology
  • Chemokine CXCL9 / metabolism
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Female
  • Giant Cell Arteritis / drug therapy
  • Giant Cell Arteritis / immunology*
  • Giant Cell Arteritis / metabolism
  • Glucocorticoids / therapeutic use
  • Granzymes / immunology
  • Granzymes / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prednisone / therapeutic use
  • Prognosis
  • Prospective Studies
  • Receptors, CXCR3 / immunology
  • Receptors, CXCR3 / metabolism

Substances

  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Cytokines
  • Glucocorticoids
  • Receptors, CXCR3
  • Granzymes
  • Prednisone