Pathogenesis of giant cell arteritis: new insight into the implication of CD161+ T cells

Clin Exp Rheumatol. 2013 Jan-Feb;31(1 Suppl 75):S65-73. Epub 2013 Apr 19.

Abstract

Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that usually affects the aorta and/or its major branches, especially the branches of the carotid arteries. Histo-pathological lesions are observed in all layers of the artery leading to segmental and focal panarteritis with a polymorphic cell infiltrate that includes T cells, macrophages and multinucleated giant cells, a fragmented internal elastic lamina and intimal hyperplasia. The pathophysiology of GCA is complex and not fully understood. In this review, we discuss the immunological aspects of GCA pathogenesis with a particular emphasis on T cell responses. Upon dendritic cell activation in the adventitia, CD4 T cells co-expressing CD161 are recruited in the arterial wall and polarised into Th1 and Th17 cells that produce IFN-γ and IL-17, respectively. These cytokines activate macrophages, giant cells and vascular smooth muscle cells, thus inducing vascular remodelling which leads to the ischaemic manifestations of GCA. Macrophages infiltrating the adventitia produce IL-1β and IL-6, which are responsible for the general symptoms encountered in GCA.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Arteries / drug effects
  • Arteries / immunology*
  • Arteries / pathology
  • Arteries / physiopathology
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Communication
  • Chemotaxis, Leukocyte
  • Giant Cell Arteritis / drug therapy
  • Giant Cell Arteritis / immunology*
  • Giant Cell Arteritis / pathology
  • Giant Cell Arteritis / physiopathology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Inflammation Mediators / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / immunology
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism*
  • Th1 Cells / immunology
  • Th17 Cells / immunology

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • IFNG protein, human
  • IL6 protein, human
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-6
  • KLRB1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily B
  • Interferon-gamma