In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes

Qizhi Tang, Kammi J. Henriksen, Mingying Bi, Erik B. Finger, Greg Szot, Jianqin Ye, Emma L. Masteller, Hugh McDevitt, Mark Bonyhadi, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

829 Citations (Scopus)

Abstract

The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ T regs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded T regs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.

Original languageEnglish (US)
Pages (from-to)1455-1465
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number11
DOIs
StatePublished - Jun 7 2004

Fingerprint

Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Autoimmunity
Antigens
Phenotype
Inbred NOD Mouse
Graft Rejection
Immunotherapy
Interleukin-2
T-Lymphocytes
Population
In Vitro Techniques

Keywords

  • Autoimnmnity
  • CD4CD25 T cells
  • Immunoregulation
  • NOD mice
  • Tolerance

Cite this

In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. / Tang, Qizhi; Henriksen, Kammi J.; Bi, Mingying; Finger, Erik B.; Szot, Greg; Ye, Jianqin; Masteller, Emma L.; McDevitt, Hugh; Bonyhadi, Mark; Bluestone, Jeffrey A.

In: Journal of Experimental Medicine, Vol. 199, No. 11, 07.06.2004, p. 1455-1465.

Research output: Contribution to journalArticle

Tang, Q, Henriksen, KJ, Bi, M, Finger, EB, Szot, G, Ye, J, Masteller, EL, McDevitt, H, Bonyhadi, M & Bluestone, JA 2004, 'In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes', Journal of Experimental Medicine, vol. 199, no. 11, pp. 1455-1465. https://doi.org/10.1084/jem.20040139
Tang, Qizhi ; Henriksen, Kammi J. ; Bi, Mingying ; Finger, Erik B. ; Szot, Greg ; Ye, Jianqin ; Masteller, Emma L. ; McDevitt, Hugh ; Bonyhadi, Mark ; Bluestone, Jeffrey A. / In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 11. pp. 1455-1465.
@article{8c035786f05e460596f0edb34269647f,
title = "In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes",
abstract = "The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ T regs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded T regs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.",
keywords = "Autoimnmnity, CD4CD25 T cells, Immunoregulation, NOD mice, Tolerance",
author = "Qizhi Tang and Henriksen, {Kammi J.} and Mingying Bi and Finger, {Erik B.} and Greg Szot and Jianqin Ye and Masteller, {Emma L.} and Hugh McDevitt and Mark Bonyhadi and Bluestone, {Jeffrey A.}",
year = "2004",
month = "6",
day = "7",
doi = "10.1084/jem.20040139",
language = "English (US)",
volume = "199",
pages = "1455--1465",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "11",

}

TY - JOUR

T1 - In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes

AU - Tang, Qizhi

AU - Henriksen, Kammi J.

AU - Bi, Mingying

AU - Finger, Erik B.

AU - Szot, Greg

AU - Ye, Jianqin

AU - Masteller, Emma L.

AU - McDevitt, Hugh

AU - Bonyhadi, Mark

AU - Bluestone, Jeffrey A.

PY - 2004/6/7

Y1 - 2004/6/7

N2 - The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ T regs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded T regs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.

AB - The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ T regs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded T regs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.

KW - Autoimnmnity

KW - CD4CD25 T cells

KW - Immunoregulation

KW - NOD mice

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=2942642383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942642383&partnerID=8YFLogxK

U2 - 10.1084/jem.20040139

DO - 10.1084/jem.20040139

M3 - Article

VL - 199

SP - 1455

EP - 1465

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 11

ER -