ICOS is essential for the development of experimental autoimmune myasthenia gravis

Benjamin G. Scott; Huan Yang; Erdem Tüzün; Chen Dong; Richard A. Flavell; Premkumar Christadoss

doi:10.1016/j.jneuroim.2004.04.019

ICOS is essential for the development of experimental autoimmune myasthenia gravis

Benjamin G. Scott, Huan Yang, Erdem Tüzün, Chen Dong, Richard A. Flavell, Premkumar Christadoss

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant α146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.

Original language	English (US)
Pages (from-to)	16-25
Number of pages	10
Journal	Journal of Neuroimmunology
Volume	153
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2004.04.019
State	Published - Aug 2004
Externally published	Yes

Keywords

AChR
APC
Ab
Autoimmunity
B7RP-1
BTX
Costimulation
EAMG
Experimental autoimmune myasthenia gravis
ICOS
Ig
Myasthenia gravis
acetylcholine receptor
antibody
antigen presenting cell
experimental autoimmune myasthenia gravis
α-bungarotoxin

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/j.jneuroim.2004.04.019

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@article{4df7756c47a745dd90695745335b3219,

title = "ICOS is essential for the development of experimental autoimmune myasthenia gravis",

abstract = "Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant α146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.",

keywords = "AChR, APC, Ab, Autoimmunity, B7RP-1, BTX, Costimulation, EAMG, Experimental autoimmune myasthenia gravis, ICOS, Ig, Myasthenia gravis, acetylcholine receptor, antibody, antigen presenting cell, experimental autoimmune myasthenia gravis, α-bungarotoxin",

author = "Scott, {Benjamin G.} and Huan Yang and Erdem T{\"u}z{\"u}n and Chen Dong and Flavell, {Richard A.} and Premkumar Christadoss",

note = "Funding Information: Huan Yang was a Myasthenia Gravis Foundation Osserman/Sosin/McClure Postdoctoral Fellowship recipient and is now an MDA Neuromuscular Disease Research Career Award recipient. Funding Information: Benjamin G. Scott was a Myasthenia Gravis Foundation Henry R. Viets Predoctoral Fellowship recipient and NIH Mucosal Immunology and Defense Training Grant recipient and is now a James W. McLaughlin Fellowship recipient. Funding Information: We would like to thank Arlene Sharpe, MD PhD, (Harvard Medical School, Boston, MA) for providing the anti-B7-1 and anti-B7-2 hybridomas, Mark Griffin, MS, for his dedicated support with flow cytometry analysis at the UTMB Flow Cytometry Core Facility, and Stephen Higgs, PhD, for his assistance with fluorescence microscopy. This study is supported by NIHR21A1049995 and the Advanced Technology Program of Texas Higher Education Coordinating Board. ",

year = "2004",

month = aug,

doi = "10.1016/j.jneuroim.2004.04.019",

language = "English (US)",

volume = "153",

pages = "16--25",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier B.V.",

number = "1-2",

}

TY - JOUR

T1 - ICOS is essential for the development of experimental autoimmune myasthenia gravis

AU - Scott, Benjamin G.

AU - Yang, Huan

AU - Tüzün, Erdem

AU - Dong, Chen

AU - Flavell, Richard A.

AU - Christadoss, Premkumar

N1 - Funding Information: Huan Yang was a Myasthenia Gravis Foundation Osserman/Sosin/McClure Postdoctoral Fellowship recipient and is now an MDA Neuromuscular Disease Research Career Award recipient. Funding Information: Benjamin G. Scott was a Myasthenia Gravis Foundation Henry R. Viets Predoctoral Fellowship recipient and NIH Mucosal Immunology and Defense Training Grant recipient and is now a James W. McLaughlin Fellowship recipient. Funding Information: We would like to thank Arlene Sharpe, MD PhD, (Harvard Medical School, Boston, MA) for providing the anti-B7-1 and anti-B7-2 hybridomas, Mark Griffin, MS, for his dedicated support with flow cytometry analysis at the UTMB Flow Cytometry Core Facility, and Stephen Higgs, PhD, for his assistance with fluorescence microscopy. This study is supported by NIHR21A1049995 and the Advanced Technology Program of Texas Higher Education Coordinating Board.

PY - 2004/8

Y1 - 2004/8

N2 - Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant α146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.

AB - Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant α146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.

KW - AChR

KW - APC

KW - Ab

KW - Autoimmunity

KW - B7RP-1

KW - BTX

KW - Costimulation

KW - EAMG

KW - Experimental autoimmune myasthenia gravis

KW - ICOS

KW - Ig

KW - Myasthenia gravis

KW - acetylcholine receptor

KW - antibody

KW - antigen presenting cell

KW - experimental autoimmune myasthenia gravis

KW - α-bungarotoxin

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U2 - 10.1016/j.jneuroim.2004.04.019

DO - 10.1016/j.jneuroim.2004.04.019

M3 - Article

C2 - 15265659

AN - SCOPUS:3242721247

SN - 0165-5728

VL - 153

SP - 16

EP - 25

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

ICOS is essential for the development of experimental autoimmune myasthenia gravis

Abstract

Keywords

ASJC Scopus subject areas

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