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Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease

Published on Sep 1, 2016in The Journal of Allergy and Clinical Immunology
· DOI :10.1016/j.jaci.2015.12.1330
Hamid Mattoo16
Estimated H-index: 16
(Harvard University),
Vinay S. Mahajan20
Estimated H-index: 20
(Harvard University)
+ 11 AuthorsShiv Pillai45
Estimated H-index: 45
(Harvard University)
Cite
Abstract
Background IgG 4 -related disease (IgG 4 -RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4 + T cells constitute the major inflammatory cell population in IgG 4 -RD lesions. Objective We used an unbiased approach to characterize CD4 + T-cell subsets in patients with IgG 4 -RD based on their clonal expansion and ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4 + effector/memory T cells in a cohort of 101 patients with IgG 4 -RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4 + SLAMF7 + cytotoxic T lymphocytes (CTLs) and CD4 + GATA3 + T H 2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. Results CD4 + effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG 4 -RD. Next-generation sequencing revealed prominent clonal expansions of these CD4 + CTLs but not CD4 + GATA3 + memory T H 2 cells in patients with IgG 4 -RD. The dominant T cells infiltrating a range of inflamed IgG 4 -RD tissue sites were clonally expanded CD4 + CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4 + CTLs. Conclusions IgG 4 -RD is prominently linked to clonally expanded IL-1β– and TGF-β1–secreting CD4 + CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4 + T cells are now linked to a human disease characterized by chronic inflammation and fibrosis.
  • References (61)
  • Citations (85)
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References61
Newest
Published on Aug 1, 2015in Journal of Virology4.32
Susan Johnson2
Estimated H-index: 2
(WRAIR: Walter Reed Army Institute of Research),
Michael A. Eller14
Estimated H-index: 14
(WRAIR: Walter Reed Army Institute of Research)
+ 13 AuthorsAlterGalit50
Estimated H-index: 50
(Harvard University)
CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcripti...
Published on Apr 1, 2015in The Lancet59.10
Terumi Kamisawa56
Estimated H-index: 56
,
Yoh Zen62
Estimated H-index: 62
(Kobe University)
+ 1 AuthorsJohn H. Stone67
Estimated H-index: 67
(Harvard University)
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions ...
Published on Sep 1, 2014in The Journal of Allergy and Clinical Immunology
Hamid Mattoo16
Estimated H-index: 16
(Harvard University),
Vinay S. Mahajan20
Estimated H-index: 20
(Harvard University)
+ 6 AuthorsShiv Pillai45
Estimated H-index: 45
(Harvard University)
Background IgG 4 -related disease (IgG 4 -RD) is a poorly understood, multiorgan, chronic inflammatory disease characterized by tumefactive lesions, storiform fibrosis, obliterative phlebitis, and accumulation of IgG 4 -expressing plasma cells at disease sites. Objective The role of B cells and IgG 4 antibodies in IgG 4 -RD pathogenesis is not well defined. We evaluated patients with IgG 4 -RD for activated B cells in both disease lesions and peripheral blood and investigated their role in disea...
Published on Jul 1, 2014in Annals of the Rheumatic Diseases14.30
Emanuel Della-Torre13
Estimated H-index: 13
(Harvard University),
Hamid Mattoo16
Estimated H-index: 16
(Harvard University)
+ 5 AuthorsJohn H. Stone67
Estimated H-index: 67
(Harvard University)
Midline destructive lesion (MDL), also known as ‘lethal midline granuloma’, represents a fibroinflammatory condition characterised by relentless erosion of the nose, paranasal sinuses and palate.1 ,2 Disease attribution remains elusive for many cases, which continue to be labelled ‘idiopathic’.2 Four patients, two males and two females, were referred because of progressive erosion of midline facial structures that had occurred over 2–3 years. Their median age was 40 years (range 27–54). Presenti...
Published on Apr 23, 2014in Frontiers in Immunology4.72
Jaime De Calisto10
Estimated H-index: 10
(BIDMC: Beth Israel Deaconess Medical Center),
Ninghai Wang21
Estimated H-index: 21
(BIDMC: Beth Israel Deaconess Medical Center)
+ 3 AuthorsCox Terhorst80
Estimated H-index: 80
(BIDMC: Beth Israel Deaconess Medical Center)
Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B cell responses. Additionally, the expression of SAP in double-positive (DP) thymocytes is mandatory for natural killer T (NKT) cells and, in mouse, for innate CD8+ T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Sla...
Published on Mar 1, 2014in Allergy6.77
Hamid Mattoo16
Estimated H-index: 16
(Harvard University),
Emanuel Della-Torre13
Estimated H-index: 13
(Harvard University)
+ 2 AuthorsShiv Pillai45
Estimated H-index: 45
(Harvard University)
IgG4 related disease (IgG4-RD) is characterized by a lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, tumefactive lesions, obliterative phlebitis, and mild to moderate eosinophilia. It has been suggested that IgG4-RD is characterized by allergic manifestations and is potentially driven by enhanced T helper type 2 (Th2) responses. We aimed to investigate the potential contribution of atopy to enhanced Th2 responses in IgG4-RD. Peripheral blood mononuclear cells from 39 patients were i...
Published on Feb 1, 2014in Allergy6.77
E. Della Torre1
Estimated H-index: 1
(Harvard University),
Hamid Mattoo16
Estimated H-index: 16
(Harvard University)
+ 3 AuthorsJohn H. Stone67
Estimated H-index: 67
(Harvard University)
IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect virtually every organ system. T helper type 2 responses have been presumed to be pathogenic in this disease and a high proportion of IgG4-RD patients are reported to have longstanding allergies, peripheral blood eosinophilia, and serum IgE elevation. It has therefore been proposed that allergic mechanisms drive IgG4-RD. However, no epidemiological assessment of atopy, peripheral blood eosinophilia, serumIgEconcentrati...
Published on Jan 24, 2014in Annual Review of Pathology-mechanisms of Disease13.83
Vinay S. Mahajan20
Estimated H-index: 20
,
Hamid Mattoo16
Estimated H-index: 16
+ 2 AuthorsJohn H. Stone67
Estimated H-index: 67
Published on Oct 1, 2013in Critical Reviews in Oncology Hematology5.01
André Veillette53
Estimated H-index: 53
(McGill University),
Huaijian Guo7
Estimated H-index: 7
(McGill University)
Abstract Signaling lymphocytic activation molecule (SLAM) family receptors have been implicated in normal immunity, immunodeficiencies and autoimmunity. CS1 (also known as CRACC, CD319 and SLAMF7) is a member of the SLAM family expressed on several normal hematopoietic cell types. It is also highly and nearly universally expressed on multiple myeloma (MM) cells. This review focuses on the biology of CS1, both in normal hematopoietic cells and in MM cells. It also discusses the preclinical and cl...
Published on Mar 1, 2013in Nature Immunology23.53
Daniel Mucida34
Estimated H-index: 34
(La Jolla Institute for Allergy and Immunology),
Mohammad Mushtaq Husain2
Estimated H-index: 2
(La Jolla Institute for Allergy and Immunology)
+ 22 AuthorsMichael J. Docherty5
Estimated H-index: 5
(UCSD: University of California, San Diego)
CD4+ and CD8+ T cells are considered distinct functional lymphocyte subsets. Cheroutre and Mucida and their colleagues show that mature gut-associated CD4+ T cells lose ThPOK expression and reactivate CD8 cytolytic effector programs.
Cited By85
Newest
Published on Jul 3, 2019in United European gastroenterology journal3.45
Heithem Soliman (Paris Diderot University), Marie-Pierre Vullierme2
Estimated H-index: 2
(Paris Diderot University)
+ 4 AuthorsVinciane Rebours23
Estimated H-index: 23
(Paris Diderot University)
Background and aimsSteroid therapy is the first-line treatment for autoimmune pancreatitis but relapses are frequent. The aims were to assess the efficacy and the safety of immunomodulator treatmen...
Published on Sep 1, 2019
Wen Zhang22
Estimated H-index: 22
(Peking Union Medical College Hospital),
John H. Stone67
Estimated H-index: 67
(Harvard University)
Summary IgG4-related disease was unrecognised as a unified disease entity until this century, yet in a short period of time the disease has been appreciated to have a worldwide distribution, and its clinical, pathological, and radiological features have been described in considerable detail. The disease has strong organ predilections, and many of the clinical presentations of disease are increasingly familiar to both generalists and specialists. Early recognition of IgG4-related disease is cruci...
Published on Jul 15, 2019in Journal of Immunology4.72
Benjamin J. Meckiff1
Estimated H-index: 1
,
Kristin Ladell27
Estimated H-index: 27
+ 5 AuthorsHeather M. Long16
Estimated H-index: 16
Published on Aug 28, 2019in Journal of Dental Research5.13
X. Hong (HKUST: Hong Kong University of Science and Technology), S.N. Min (PKU: Peking University)+ 6 AuthorsH.Y. Yang (HKUST: Hong Kong University of Science and Technology)
IgG4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic fibroinflammatory disease that affects salivary glands and leads to hyposalivation. Tumor necrosis factor–α (TNF-α...
Published on Jan 1, 2019in International Journal of Oral and Maxillofacial Surgery1.96
Takashi Maehara16
Estimated H-index: 16
(Kyushu University),
Shiv Pillai45
Estimated H-index: 45
(Harvard University)
+ 1 AuthorsSeiji Nakamura33
Estimated H-index: 33
(Kyushu University)
Abstract Immunoglobulin G4-related disease (IgG4-RD), recognized only recently as a single diagnostic entity, is a chronic inflammatory condition of unknown etiology. The diagnosis of IgG4-RD relies heavily on histopathological analysis and the correlation of histology findings with clinical, serological, and radiological data. CD4 + T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations in IgG4-RD and are believed to cause organ damage and tiss...
Published on Jul 1, 2019in The Journal of Allergy and Clinical Immunology
Emanuel Della-Torre13
Estimated H-index: 13
(UniSR: Vita-Salute San Raffaele University),
Elena Rigamonti7
Estimated H-index: 7
(UniSR: Vita-Salute San Raffaele University)
+ 16 AuthorsRaffaella Milani18
Estimated H-index: 18
Abstract Background IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in IgG4-RD. Methods Total circulating CD19 + B-lymphocytes, naive B cells, memory B cells, or plasmablasts from IgG4-RD...
Published on Jun 1, 2019
Constanze H. Waggershauser1
Estimated H-index: 1
,
Martin Storr1
Estimated H-index: 1
Published on Jun 1, 2019in Seminars in Arthritis and Rheumatism5.07
Jungen Tang (HUST: Huazhong University of Science and Technology), Shaozhe Cai (HUST: Huazhong University of Science and Technology)+ 1 AuthorsLingli Dong12
Estimated H-index: 12
(HUST: Huazhong University of Science and Technology)
Abstract Objective ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring disease activity, and predicting prognosis and response to therapy. Here, we review the recent development and identification of biomarkers for IgG4-RD. Methods Through extensive literature review and analysis, we updated the biomarkers for IgG4-RD and further put forward our own viewpoints. Results In addition to t...
Published on Oct 15, 2018in Nephrology Dialysis Transplantation4.20
Takahiro Kawakami3
Estimated H-index: 3
(Kanazawa University),
Ichiro Mizushima11
Estimated H-index: 11
(Kanazawa University)
+ 7 AuthorsMitsuhiro Kawano29
Estimated H-index: 29
(Kanazawa University)
Published on May 1, 2019in Rheumatology5.15
Liwen Wang1
Estimated H-index: 1
(THU: Tsinghua University),
Panpan Zhang3
Estimated H-index: 3
(Peking Union Medical College Hospital)
+ 16 AuthorsHua Chen17
Estimated H-index: 17
(Peking Union Medical College Hospital)
View next paperIgG4-related disease.