An Uneven Expression of T Cell Receptor V Genes in the Arterial Wall and Peripheral Blood in Giant Cell Arteritis

Schaufelberger, C.; Andersson, Rune; Nordborg, E; Hansson, Göran K.; Nordborg, Claes; Wahlström, Jan

doi:10.1007/s10753-008-9088-9

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…The identity of this antigen remains elusive. A recent immunophenotypic analysis has provided evidence supporting these earlier studies via a comparison of the T-cell receptor usage in peripheral blood lymphocytes with that of the lesion infiltrates in GCA patients at the time of diagnosis [14]. Disparities in the TCR V gene expansions in peripheral blood lymphocytes and tissue lymphocytes point to the possibility of a selective T-cell recruitment process or local expansion of T cells in situ.…”

Section: Adaptive Immune Responses In the Unique Environment Of The Amentioning

confidence: 83%

Vascular damage in giant cell arteritis

et al. 2009

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Immune-mediated damage to medium-sized arteries results in wall remodeling with intimal hyperplasia, luminal stenosis and tissue ischemia. In the case of the aorta, vasculitis may result in dissection, aneurysm or rupture. The response-to-injury program of the blood vessel is a concerted action between the immune system and wall-resident cells, involving the release of growth and angiogenic factors from macrophages and giant cells and the migration and hyperproliferation of vascular smooth muscle cells. Innate immune cells, specifically, dendritic cells (DC) positioned in the vessel wall, have been implicated in the earliest steps of vasculitis. Pathogen-derived molecular patterns are capable of activating vascular DC and initiating adaptive immune responses. The pattern of the emerging vessel wall inflammation is ultimately determined by the initial insult. Ligands to toll-like receptor (TLR) 4, such as lipopolysaccharides, facilitate the recruitment of CD4 T cells that invade deep into the wall and distribute in a panarteritic pattern. Conversely, ligands for TLR5 condition vascular DC to support perivasculitic infiltrates. In essence, both innate and adaptive immune reactions collaborate to render the arterial wall susceptible to inflammatory damage. Unique features of the tissue microenvironment, including specialized DC, shape the course of the inflammatory response. Differences in vascular damage pattern encountered in different patients may relate to distinct instigators of vasculitis.

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Section: Adaptive Immune Responses In the Unique Environment Of The Amentioning

confidence: 83%

Vascular damage in giant cell arteritis

et al. 2009

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“…Antigen imposes a high selection pressure and drives the expansion of selected T cells, yet frequencies of antigen-specific T cells only reach 1 in 1,000 to 1 in 10,000 cells. Studies focusing on T cell receptor V genes in the arterial wall and the peripheral blood of GCA patients have arrived at the conclusion that the T cell repertoire is biased [14,15]. Sequence analysis of CD4 T cells isolated from the inflamed temporal arteries has strongly supported local T cell activation and expansion of only a few selected T cell specificities.…”

Section: Ifn-γ-producing Th1 Cells In Gcamentioning

confidence: 99%

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

Weyand

Younge

Goronzy

2011

Current Opinion in Rheumatology

130

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Purpose of review Granuloma formation in giant cell arteritis (GCA) emphasizes the role of the 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 eightfold, 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 (APC), 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.

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“…The authors state that this difference may be due to local expansion of T cells caused by either recruitment of specific T cells or local proliferation of these T cells. In this study, no distinction could be made between TCR genes of CD4+ and CD8+ T cells in vascular tissues (75). Most importantly, patients and controls in these studies investigating TCR diversity were not controlled for CMV status or matched for HLA polymorphisms, factors associated with TCR diversity (76).…”

Section: Phenotype Of Cd8+ T Cells In Circulation and Affected Tissuementioning

confidence: 92%

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

et al. 2021

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Vasculitis refers to inflammation of blood vessels and can cause a variety of serious complications depending on which vessels are affected. Two different forms of vasculitis are Giant Cell Arteritis (GCA) and Granulomatosis with Polyangiitis (GPA). GCA is the most common form of vasculitis in adults affecting the large arteries and can lead to visual impairment and development of aneurysms. GPA affects small- and medium-sized blood vessels predominantly in the lungs and kidneys resulting in organ failure. Both diseases can potentially be fatal. Although the pathogenesis of GCA and GPA are incompletely understood, a prominent role for CD4+ T cells has been implicated in both diseases. More recently, the role of CD8+ T cells has gained renewed interest. CD8+ T cells are important players in the adaptive immune response against intracellular microorganisms. After a general introduction on the different forms of vasculitis and their association with infections and CD8+ T cells, we review the current knowledge on CD8+ T-cell involvement in the immunopathogenesis of GCA and GPA focusing on phenotypic and functional features of circulating and lesional CD8+ T cells. Furthermore, we discuss to which extent aging is associated with CD8+ T-cell phenotype and function in GCA and GPA.

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An Uneven Expression of T Cell Receptor V Genes in the Arterial Wall and Peripheral Blood in Giant Cell Arteritis

Cited by 10 publications

References 46 publications

Vascular damage in giant cell arteritis

Vascular damage in giant cell arteritis

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

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

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