The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Uraushihara, K.
Right arrow Articles by Watanabe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Uraushihara, K.
Right arrow Articles by Watanabe, M.
The Journal of Immunology, 2003, 171: 708-716.
Copyright © 2003 by The American Association of Immunologists

Regulation of Murine Inflammatory Bowel Disease by CD25+ and CD25- CD4+ Glucocorticoid-Induced TNF Receptor Family-Related Gene+ Regulatory T Cells1

Koji Uraushihara2,{dagger}, Takanori Kanai2,3,{dagger}, Kwibeom Ko*, Teruji Totsuka{dagger}, Shin Makita{dagger}, Ryoichi Iiyama{dagger}, Tetsuya Nakamura{dagger} and Mamoru Watanabe{dagger}

* Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; and {dagger} Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

CD4+CD25+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance and prevention of autoimmune disease. However, accumulating evidence suggests that a fraction of the peripheral CD4+CD25- T cell population also possesses regulatory activity in vivo. Recently, it has been shown glucocorticoid-induced TNFR family-related gene (GITR) is predominantly expressed on CD4+CD25+ regulatory T cells. In this study, we show evidence that CD4+GITR+ T cells, regardless of the CD25 expression, regulate the mucosal immune responses and intestinal inflammation. SCID mice restored with the CD4+GITR- T cell population developed wasting disease and severe chronic colitis. Cotransfer of CD4+GITR+ population prevented the development of CD4+CD45RBhigh T cell-transferred colitis. Administration of anti-GITR mAb-induced chronic colitis in mice restored both CD45RBhigh and CD45RBlow CD4+ T cells. Interestingly, both CD4+CD25+ and CD4+CD25- GITR+ T cells prevented wasting disease and colitis. Furthermore, in vitro studies revealed that CD4+CD25-GITR+ T cells as well as CD4+CD25+GITR+ T cells expressed CTLA-4 intracellularly, showed anergic, suppressed T cell proliferation, and produced IL-10 and TGF-{beta}. These data suggest that GITR can be used as a specific marker for regulatory T cells controlling mucosal inflammation and also as a target for treatment of inflammatory bowel disease.




This article has been cited by other articles:


Home page
 BloodHome page
M. M. Collazo, D. Wood, K. H. T. Paraiso, E. Lund, R. W. Engelman, C.-T. Le, D. Stauch, K. Kotsch, and W. G. Kerr
SHIP limits immunoregulatory capacity in the T-cell compartment
Blood, March 26, 2009; 113(13): 2934 - 2944.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Gereke, S. Jung, J. Buer, and D. Bruder
Alveolar Type II Epithelial Cells Present Antigen to CD4+ T Cells and Induce Foxp3+ Regulatory T Cells
Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 344 - 355.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Ito, T. Kanai, T. Totsuka, R. Okamoto, K. Tsuchiya, Y. Nemoto, A. Yoshioka, T. Tomita, T. Nagaishi, N. Sakamoto, et al.
Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G199 - G207.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
A. Boasso, M. Vaccari, A. Hryniewicz, D. Fuchs, J. Nacsa, V. Cecchinato, J. Andersson, G. Franchini, G. M. Shearer, and C. Chougnet
Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection
J. Virol., November 1, 2007; 81(21): 11593 - 11603.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. Tuyaerts, S. Van Meirvenne, A. Bonehill, C. Heirman, J. Corthals, H. Waldmann, K. Breckpot, K. Thielemans, and J. L. Aerts
Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells
J. Leukoc. Biol., July 1, 2007; 82(1): 93 - 105.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. P. Hilchey, A. De, L. M. Rimsza, R. B. Bankert, and S. H. Bernstein
Follicular Lymphoma Intratumoral CD4+CD25+GITR+ Regulatory T Cells Potently Suppress CD3/CD28-Costimulated Autologous and Allogeneic CD8+CD25- and CD4+CD25- T Cells
J. Immunol., April 1, 2007; 178(7): 4051 - 4061.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
J. S. Ahn, D. K. Krishnadas, and B. Agrawal
Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood
Int. Immunol., March 1, 2007; 19(3): 227 - 237.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
L Santucci, M Agostini, S Bruscoli, A Mencarelli, S Ronchetti, E Ayroldi, A Morelli, M Baldoni, and C Riccardi
GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice
Gut, January 1, 2007; 56(1): 52 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Metwali, T. Setiawan, A. M. Blum, J. Urban, D. E. Elliott, L. Hang, and J. V. Weinstock
Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection.
Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G253 - G259.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Ramirez-Montagut, A. Chow, D. Hirschhorn-Cymerman, T. H. Terwey, A. A. Kochman, S. Lu, R. C. Miles, S. Sakaguchi, A. N. Houghton, and M. R. M. van den Brink
Glucocorticoid-Induced TNF Receptor Family Related Gene Activation Overcomes Tolerance/Ignorance to Melanoma Differentiation Antigens and Enhances Antitumor Immunity.
J. Immunol., June 1, 2006; 176(11): 6434 - 6442.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. L. Every, D. R. Kramer, S. I. Mannering, A. M. Lew, and L. C. Harrison
Intranasal Vaccination with Proinsulin DNA Induces Regulatory CD4+ T Cells That Prevent Experimental Autoimmune Diabetes.
J. Immunol., April 15, 2006; 176(8): 4608 - 4615.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Ono, J. Shimizu, Y. Miyachi, and S. Sakaguchi
Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Proteinhigh, Foxp3-Expressing CD25+ and CD25- Regulatory T Cells.
J. Immunol., April 15, 2006; 176(8): 4748 - 4756.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. J. Kim, H. Y. Kim, B. K. Kim, S. Kim, and D. H. Chung
Engagement of Glucocorticoid-Induced TNF Receptor Costimulates NKT Cell Activation In Vitro and In Vivo
J. Immunol., March 15, 2006; 176(6): 3507 - 3515.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Veldman, A. Pahl, S. Beissert, W. Hansen, J. Buer, D. Dieckmann, G. Schuler, and M. Hertl
Inhibition of the transcription factor foxp3 converts desmoglein 3-specific type 1 regulatory T cells into th2-like cells.
J. Immunol., March 1, 2006; 176(5): 3215 - 3222.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
U G Strauch, F Obermeier, N Grunwald, S Gurster, N Dunger, M Schultz, D P Griese, M Mahler, J Scholmerich, and H C Rath
Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis
Gut, November 1, 2005; 54(11): 1546 - 1552.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Cuzzocrea, E. Ayroldi, R. Di Paola, M. Agostini, E. Mazzon, S. Bruscoli, T. Genovese, S. Ronchetti, A. P. Caputi, and C. Riccardi
Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis
FASEB J, August 1, 2005; 19(10): 1253 - 1265.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
K. S. Lee, G. Sen, and C. M. Snapper
Endogenous CD4+ CD25+ Regulatory T Cells Play No Apparent Role in the Acute Humoral Response to Intact Streptococcus pneumoniae
Infect. Immun., July 1, 2005; 73(7): 4427 - 4431.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. M. Esparza and R. H. Arch
Glucocorticoid-Induced TNF Receptor Functions as a Costimulatory Receptor That Promotes Survival in Early Phases of T Cell Activation
J. Immunol., June 15, 2005; 174(12): 7869 - 7874.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
K. M. Thorstenson, L. Herzovi, and A. Khoruts
A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo
Int. Immunol., April 1, 2005; 17(4): 335 - 342.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Shimizu, R. Iida, Y. Sato, E. Moriizumi, A. Nishikawa, and Y. Ishida
Cross-Linking of CD45 on Suppressive/Regulatory T Cells Leads to the Abrogation of Their Suppressive Activity In Vitro
J. Immunol., April 1, 2005; 174(7): 4090 - 4097.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
H. He, R. J. Messer, S. Sakaguchi, G. Yang, S. J. Robertson, and K. J. Hasenkrug
Reduction of Retrovirus-Induced Immunosuppression by In Vivo Modulation of T Cells during Acute Infection
J. Virol., November 1, 2004; 78(21): 11641 - 11647.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. L. Stephens, R. S. McHugh, M. J. Whitters, D. A. Young, D. Luxenberg, B. M. Carreno, M. Collins, and E. M. Shevach
Engagement of Glucocorticoid-Induced TNFR Family-Related Receptor on Effector T Cells by its Ligand Mediates Resistance to Suppression by CD4+CD25+ T Cells
J. Immunol., October 15, 2004; 173(8): 5008 - 5020.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. J. Kim, Z. Li, R. N. Fariss, D. F. Shen, S. P. Mahesh, C. Egwuagu, C.-R. Yu, C. N. Nagineni, C.-C. Chan, and R. B. Nussenblatt
Constitutive and Cytokine-Induced GITR Ligand Expression on Human Retinal Pigment Epithelium and Photoreceptors
Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3170 - 3176.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Makita, T. Kanai, S. Oshima, K. Uraushihara, T. Totsuka, T. Sawada, T. Nakamura, K. Koganei, T. Fukushima, and M. Watanabe
CD4+CD25bright T Cells in Human Intestinal Lamina Propria as Regulatory Cells
J. Immunol., September 1, 2004; 173(5): 3119 - 3130.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
H.-B. Park, D.-J. Paik, E. Jang, S. Hong, and J. Youn
Acquisition of anergic and suppressive activities in transforming growth factor-{beta}-costimulated CD4+CD25- T cells
Int. Immunol., August 1, 2004; 16(8): 1203 - 1213.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
S. J. Muriglan, T. Ramirez-Montagut, O. Alpdogan, T. W. van Huystee, J. M. Eng, V. M. Hubbard, A. A. Kochman, K. H. Tjoe, C. Riccardi, P. P. Pandolfi, et al.
GITR Activation Induces an Opposite Effect on Alloreactive CD4+ and CD8+ T Cells in Graft-Versus-Host Disease
J. Exp. Med., July 19, 2004; 200(2): 149 - 157.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Veldman, A. Hohne, D. Dieckmann, G. Schuler, and M. Hertl
Type I Regulatory T Cells Specific for Desmoglein 3 Are More Frequently Detected in Healthy Individuals than in Patients with Pemphigus Vulgaris
J. Immunol., May 15, 2004; 172(10): 6468 - 6475.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. P. Kohm, J. S. Williams, and S. D. Miller
Cutting Edge: Ligation of the Glucocorticoid-Induced TNF Receptor Enhances Autoreactive CD4+ T Cell Activation and Experimental Autoimmune Encephalomyelitis
J. Immunol., April 15, 2004; 172(8): 4686 - 4690.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
G. J. Prud'homme
Altering immune tolerance therapeutically: the power of negative thinking
J. Leukoc. Biol., April 1, 2004; 75(4): 586 - 599.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
L. A. Stephens, A. N. Barclay, and D. Mason
Phenotypic characterization of regulatory CD4+CD25+ T cells in rats
Int. Immunol., February 1, 2004; 16(2): 365 - 375.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.