Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction: Implications for treatment of immune thrombocytopenic purpura

Masataka Kuwana, Yutaka Kawakami, Yasuo Ikeda

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb/IIIa (GPIIb/IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb/IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb/IIIa. Repeated antigenic stimulation of GPIIb/IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb/IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low interferon γ and high interleukin 10 and suppressed anti-GPIIb/IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function and could be a therapeutic option for suppressing pathogenic autoimmune responses in patients with ITP.

Original languageEnglish
Pages (from-to)621-623
Number of pages3
JournalBlood
Volume101
Issue number2
DOIs
Publication statusPublished - 2003 Jan 15

Fingerprint

Platelet Glycoprotein GPIIb-IIIa Complex
Idiopathic Thrombocytopenic Purpura
T-cells
T-Lymphocytes
Antibody Formation
Monoclonal Antibodies
Antibodies
Therapeutics
Cell Line
Autoantigens
Regulatory T-Lymphocytes
Immunosuppressive Agents
Autoimmunity
Interleukin-10
Interferons
Cell proliferation
Blood Cells
Cell culture
Cell Culture Techniques
Cell Proliferation

ASJC Scopus subject areas

  • Hematology

Cite this

Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction : Implications for treatment of immune thrombocytopenic purpura. / Kuwana, Masataka; Kawakami, Yutaka; Ikeda, Yasuo.

In: Blood, Vol. 101, No. 2, 15.01.2003, p. 621-623.

Research output: Contribution to journalArticle

@article{ffc027b108aa4b0d80b3977a2daf875a,
title = "Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction: Implications for treatment of immune thrombocytopenic purpura",
abstract = "The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb/IIIa (GPIIb/IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb/IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb/IIIa. Repeated antigenic stimulation of GPIIb/IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb/IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low interferon γ and high interleukin 10 and suppressed anti-GPIIb/IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function and could be a therapeutic option for suppressing pathogenic autoimmune responses in patients with ITP.",
author = "Masataka Kuwana and Yutaka Kawakami and Yasuo Ikeda",
year = "2003",
month = "1",
day = "15",
doi = "10.1182/blood-2002-07-2157",
language = "English",
volume = "101",
pages = "621--623",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction

T2 - Implications for treatment of immune thrombocytopenic purpura

AU - Kuwana, Masataka

AU - Kawakami, Yutaka

AU - Ikeda, Yasuo

PY - 2003/1/15

Y1 - 2003/1/15

N2 - The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb/IIIa (GPIIb/IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb/IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb/IIIa. Repeated antigenic stimulation of GPIIb/IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb/IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low interferon γ and high interleukin 10 and suppressed anti-GPIIb/IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function and could be a therapeutic option for suppressing pathogenic autoimmune responses in patients with ITP.

AB - The potential immunosuppressive effect of an anti-CD154 monoclonal antibody (mAb) on the pathogenic autoreactive T-cell response was evaluated using an in vitro culture system with glycoprotein IIb/IIIa (GPIIb/IIIa)-reactive T cells from patients with immune thrombocytopenic purpura (ITP). The anti-CD154 mAb did not inhibit T-cell proliferation, but suppressed anti-GPIIb/IIIa antibody production, in bulk peripheral blood mononuclear cell cultures stimulated with GPIIb/IIIa. Repeated antigenic stimulation of GPIIb/IIIa-reactive CD4+ T-cell lines in the presence of anti-CD154 mAb resulted in the loss of proliferative capacity and helper function for promoting anti-GPIIb/IIIa antibody production. These anergic T-cell lines showed a cytokine profile of low interferon γ and high interleukin 10 and suppressed anti-GPIIb/IIIa antibody production. Our results indicate that blockade of the CD40/CD154 interaction induces generation of autoantigen-specific anergic CD4+ T cells with regulatory function and could be a therapeutic option for suppressing pathogenic autoimmune responses in patients with ITP.

UR - http://www.scopus.com/inward/record.url?scp=0037438507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037438507&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-07-2157

DO - 10.1182/blood-2002-07-2157

M3 - Article

C2 - 12393517

AN - SCOPUS:0037438507

VL - 101

SP - 621

EP - 623

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -