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IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis

Weyand, Cornelia Ma; Younge, Brian Rb; Goronzy, Jörg Ja

Current Opinion in Rheumatology: January 2011 - Volume 23 - Issue 1 - p 43–49
doi: 10.1097/BOR.0b013e32833ee946
Vasculitis syndromes: Edited by Carlo Salvarani

Purpose of review Granuloma formation in giant cell arteritis (GCA) emphasizes the role of adaptive immunity and highlights the role of antigen-specific T cells. Recent data demonstrate that at least two separate lineages of CD4 T cells participate in vascular inflammation, providing an important clue that multiple disease instigators may initiate pathogenic immunity.

Recent finding IFN-γ-producing Th1 cells and IL-17-producing Th17 cells have been implicated in GCA. Patients with biopsy-positive GCA underwent two consecutive temporal artery biopsies, one prior to therapy and one while on corticosteroids. In untreated patients, Th1 and Th17 cells co-existed in the vascular lesions. Following therapy, Th17 cells were essentially lost, whereas Th1 cells persisted almost unaffected. In the peripheral blood of untreated patients Th17 frequencies were increased eight-fold, but normalized with therapy. Blood Th1 cells were doubled in frequency, independent of therapy. Corticosteroids functioned by selectively suppressing IL-1β, IL-6 and IL-23-releasing antigen-presenting cells (APCs), disrupting induction of Th17 cells.

Summary At least two distinct CD4 T-cell subsets promote vascular inflammation in GCA. In early disease, APCs promote differentiation of Th17 as well as Th1 cells. Chronic disease is characterized by persistent Th1-inducing signals, independent of IL-17-mediated inflammation. More than one disease instigator may trigger APCs to induce multiple T-cell lineages. Cocktails of therapies will be needed for appropriate disease control.

aDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA

bDepartment of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA

Correspondence to Cornelia M. Weyand, MD, PhD, Department of Medicine: Immunology and Rheumatology, Stanford University School of Medicine, Center for Clinical Sciences Research, 269 Campus Drive West, Stanford, CA 94305-5166, USA Tel: +1 650 723 9027; fax: +1 650 723 7509; e-mail: cweyand@stanford.edu

© 2011 Lippincott Williams & Wilkins, Inc.