Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis

Ype P. de Jong, Svend T. Rietdijk, William Alvis Faubion, Ana C. Abadia-Molina, Kareem Clarke, Emiko Mizoguchi, Jane Tian, Tracy Delaney, Stephen Manning, Jose Carlos Gutierrez-Ramos, Atul K. Bhan, Anthony J. Coyle, Cox Terhorst

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Several autoimmune disease models depend on an imbalance in the activation of aggressor Th1 and CD4+CD25+ regulatory T (Treg) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RBhi T cells alone or in combination with CD4+CD25+ T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient Th1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to Th1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor Th1 cells, and that CD28 is required for Treg cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalInternational Immunology
Volume16
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Inducible T-Cell Co-Stimulator Protein
Regulatory T-Lymphocytes
Colitis
Th1 Cells
T-Lymphocytes
Inflammatory Bowel Diseases
Autoimmune Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis. / de Jong, Ype P.; Rietdijk, Svend T.; Faubion, William Alvis; Abadia-Molina, Ana C.; Clarke, Kareem; Mizoguchi, Emiko; Tian, Jane; Delaney, Tracy; Manning, Stephen; Gutierrez-Ramos, Jose Carlos; Bhan, Atul K.; Coyle, Anthony J.; Terhorst, Cox.

In: International Immunology, Vol. 16, No. 2, 02.2004, p. 205-213.

Research output: Contribution to journalArticle

de Jong, YP, Rietdijk, ST, Faubion, WA, Abadia-Molina, AC, Clarke, K, Mizoguchi, E, Tian, J, Delaney, T, Manning, S, Gutierrez-Ramos, JC, Bhan, AK, Coyle, AJ & Terhorst, C 2004, 'Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis', International Immunology, vol. 16, no. 2, pp. 205-213. https://doi.org/10.1093/intimm/dxh019
de Jong, Ype P. ; Rietdijk, Svend T. ; Faubion, William Alvis ; Abadia-Molina, Ana C. ; Clarke, Kareem ; Mizoguchi, Emiko ; Tian, Jane ; Delaney, Tracy ; Manning, Stephen ; Gutierrez-Ramos, Jose Carlos ; Bhan, Atul K. ; Coyle, Anthony J. ; Terhorst, Cox. / Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis. In: International Immunology. 2004 ; Vol. 16, No. 2. pp. 205-213.
@article{e61ce9d3ded9455ca2d8642d3259f546,
title = "Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis",
abstract = "Several autoimmune disease models depend on an imbalance in the activation of aggressor Th1 and CD4+CD25+ regulatory T (Treg) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RBhi T cells alone or in combination with CD4+CD25+ T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient Th1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to Th1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor Th1 cells, and that CD28 is required for Treg cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.",
author = "{de Jong}, {Ype P.} and Rietdijk, {Svend T.} and Faubion, {William Alvis} and Abadia-Molina, {Ana C.} and Kareem Clarke and Emiko Mizoguchi and Jane Tian and Tracy Delaney and Stephen Manning and Gutierrez-Ramos, {Jose Carlos} and Bhan, {Atul K.} and Coyle, {Anthony J.} and Cox Terhorst",
year = "2004",
month = "2",
doi = "10.1093/intimm/dxh019",
language = "English (US)",
volume = "16",
pages = "205--213",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis

AU - de Jong, Ype P.

AU - Rietdijk, Svend T.

AU - Faubion, William Alvis

AU - Abadia-Molina, Ana C.

AU - Clarke, Kareem

AU - Mizoguchi, Emiko

AU - Tian, Jane

AU - Delaney, Tracy

AU - Manning, Stephen

AU - Gutierrez-Ramos, Jose Carlos

AU - Bhan, Atul K.

AU - Coyle, Anthony J.

AU - Terhorst, Cox

PY - 2004/2

Y1 - 2004/2

N2 - Several autoimmune disease models depend on an imbalance in the activation of aggressor Th1 and CD4+CD25+ regulatory T (Treg) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RBhi T cells alone or in combination with CD4+CD25+ T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient Th1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to Th1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor Th1 cells, and that CD28 is required for Treg cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.

AB - Several autoimmune disease models depend on an imbalance in the activation of aggressor Th1 and CD4+CD25+ regulatory T (Treg) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RBhi T cells alone or in combination with CD4+CD25+ T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient Th1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to Th1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor Th1 cells, and that CD28 is required for Treg cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.

UR - http://www.scopus.com/inward/record.url?scp=10744229150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744229150&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxh019

DO - 10.1093/intimm/dxh019

M3 - Article

VL - 16

SP - 205

EP - 213

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 2

ER -