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


RESULTS
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.


CONCLUSIONS
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.
Weyand
Cornelia M
CM
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305-5166, USA. cweyand@stanford.edu
Younge
Brian R
BR
Goronzy
Jörg J
JJ
D056704:Adaptive Immunity; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D051193:Toll-Like Receptors / Q000276:immunology
D000305:Adrenal Cortex Hormones; D020381:Interleukin-17; D051193:Toll-Like Receptors; D007371:Interferon-gamma
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