Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis.
Giant cell arteritis is an autoimmune disease defined by explicit tissue tropism to the walls of medium and large arteries. Pathognomic inflammatory lesions are granulomatous in nature, emphasizing the functional role of CD4T cells and macrophages. Evidence for a pathogenic role of antibodies and immune complexes is missing. Analysis of T cell populations in giant cell arteritis, both in the tissue lesions and in the circulation, has supported a model of broad, polyclonal T cell activation, involving an array of functional T cell lineages. The signature of T cell cytokines produced by vasculitic lesions is typically multifunctional, including IL-2, IFN-γ, IL-17, IL-21, and GM-CSF, supportive for a general defect in T cell regulation. Recent data describing the lack of a lymph node-based population of anti-inflammatory T cells in giant cell arteritis patients offers a fresh look at the immunopathology of this vasculitis. Due to defective CD8+NOX2+regulatory T cells, giant cell arteritis patients appear unable to curtail clonal expansion within the CD4T cell compartment, resulting in widespread CD4T cell hyperimmunity. Why unopposed expansion of committed CD4 effector T cells would lead to invasion of the walls of medium and large arteries needs to be explored in further investigations.
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Ryu
R
Watanabe
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Ebru
E
Hosgur
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Hui
H
Zhang
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Zhenke
Z
Wen
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Gerald
G
Berry
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jörg J
JJ
Goronzy
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cweyand@stanford.edu.
Cornelia M
CM
Weyand
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D013700:Giant Cell Arteritis / Q000276:immunology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000276:immunology*
Anti-inflammatory T cells; CD8(+) Treg cells; Giant cell arteritis; Macrophage; Pro-inflammatory T cells
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