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

Hamid Mattoo, Vinay S. Mahajan, takashi maehara, Vikram Deshpande, Emanuel Della-Torre, Zachary S. Wallace, Maria Kulikova, Jefte M. Drijvers, Joe Daccache, Mollie N. Carruthers, Flavia V. Castelino, James R. Stone, John H. Stone, Shiv Pillai

研究成果: ジャーナルへの寄稿記事

87 引用 (Scopus)

抄録

Background IgG4-related disease (IgG4-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 IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T-cell subsets in patients with IgG4-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 IgG4-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+ TH2 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 IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4+ CTLs but not CD4+GATA3+ memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-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 IgG4-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.

元の言語英語
ページ(範囲)825-838
ページ数14
ジャーナルJournal of Allergy and Clinical Immunology
138
発行部数3
DOI
出版物ステータス出版済み - 9 1 2016
外部発表Yes

Fingerprint

Cytotoxic T-Lymphocytes
Immunoglobulin G
Interleukin-1
Flow Cytometry
T-Cell Receptor Genes
Granzymes
Aptitude
Gene Flow
T-Lymphocyte Subsets
Fibrosis
B-Lymphocytes
Chronic Disease
Cytokines
Inflammation
Phenotype
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease. / Mattoo, Hamid; Mahajan, Vinay S.; maehara, takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S.; Kulikova, Maria; Drijvers, Jefte M.; Daccache, Joe; Carruthers, Mollie N.; Castelino, Flavia V.; Stone, James R.; Stone, John H.; Pillai, Shiv.

:: Journal of Allergy and Clinical Immunology, 巻 138, 番号 3, 01.09.2016, p. 825-838.

研究成果: ジャーナルへの寄稿記事

Mattoo, H, Mahajan, VS, maehara, T, Deshpande, V, Della-Torre, E, Wallace, ZS, Kulikova, M, Drijvers, JM, Daccache, J, Carruthers, MN, Castelino, FV, Stone, JR, Stone, JH & Pillai, S 2016, 'Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease', Journal of Allergy and Clinical Immunology, 巻. 138, 番号 3, pp. 825-838. https://doi.org/10.1016/j.jaci.2015.12.1330
Mattoo, Hamid ; Mahajan, Vinay S. ; maehara, takashi ; Deshpande, Vikram ; Della-Torre, Emanuel ; Wallace, Zachary S. ; Kulikova, Maria ; Drijvers, Jefte M. ; Daccache, Joe ; Carruthers, Mollie N. ; Castelino, Flavia V. ; Stone, James R. ; Stone, John H. ; Pillai, Shiv. / Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease. :: Journal of Allergy and Clinical Immunology. 2016 ; 巻 138, 番号 3. pp. 825-838.
@article{dc749e47a3974513879b9cadd063d9e5,
title = "Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease",
abstract = "Background IgG4-related disease (IgG4-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 IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T-cell subsets in patients with IgG4-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 IgG4-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+ TH2 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 IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4+ CTLs but not CD4+GATA3+ memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-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 IgG4-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.",
author = "Hamid Mattoo and Mahajan, {Vinay S.} and takashi maehara and Vikram Deshpande and Emanuel Della-Torre and Wallace, {Zachary S.} and Maria Kulikova and Drijvers, {Jefte M.} and Joe Daccache and Carruthers, {Mollie N.} and Castelino, {Flavia V.} and Stone, {James R.} and Stone, {John H.} and Shiv Pillai",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.jaci.2015.12.1330",
language = "English",
volume = "138",
pages = "825--838",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease

AU - Mattoo, Hamid

AU - Mahajan, Vinay S.

AU - maehara, takashi

AU - Deshpande, Vikram

AU - Della-Torre, Emanuel

AU - Wallace, Zachary S.

AU - Kulikova, Maria

AU - Drijvers, Jefte M.

AU - Daccache, Joe

AU - Carruthers, Mollie N.

AU - Castelino, Flavia V.

AU - Stone, James R.

AU - Stone, John H.

AU - Pillai, Shiv

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background IgG4-related disease (IgG4-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 IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T-cell subsets in patients with IgG4-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 IgG4-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+ TH2 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 IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4+ CTLs but not CD4+GATA3+ memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-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 IgG4-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.

AB - Background IgG4-related disease (IgG4-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 IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T-cell subsets in patients with IgG4-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 IgG4-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+ TH2 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 IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4+ CTLs but not CD4+GATA3+ memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-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 IgG4-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.

UR - http://www.scopus.com/inward/record.url?scp=84960156164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960156164&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2015.12.1330

DO - 10.1016/j.jaci.2015.12.1330

M3 - Article

VL - 138

SP - 825

EP - 838

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -