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 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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kohm, A. P.
Right arrow Articles by Miller, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kohm, A. P.
Right arrow Articles by Miller, S. D.
The Journal of Immunology, 2004, 172: 4686-4690.
Copyright © 2004 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Ligation of the Glucocorticoid-Induced TNF Receptor Enhances Autoreactive CD4+ T Cell Activation and Experimental Autoimmune Encephalomyelitis1

Adam P. Kohm, Julie S. Williams and Stephen D. Miller2

Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611

The glucocorticoid-induced TNFR (GITR) is expressed at high levels on resting CD4+CD25+ T regulatory (TR) cells and regulates their suppressive phenotype. Accordingly, we show that anti-GITR mAb treatment of SJL mice with proteolipid protein 139–151-induced experimental autoimmune encephalomyelitis significantly exacerbated clinical disease severity and CNS inflammation, and induced elevated levels of Ag-specific T cell proliferation and cytokine production. Interestingly, prior depletion of TR cells failed to result in exacerbated experimental autoimmune encephalomyelitis suggesting alternative targets for the anti-GITR mAb treatment. Importantly, naive CD4+CD25− T cells up-regulated GITR expression in an activation-dependent manner and anti-GITR mAb treatment enhanced the level of CD4+ T cell activation, proliferation, and cytokine production in the absence of TR cells both in vivo and in vitro. Taken together, these findings suggest a dual functional role for GITR as GITR cross-linking both inactivates TR cells and increases CD4+CD25− T cell effector function, thus enhancing T cell immunity.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Zhou, X. Song, A. Berezov, G. Zhang, Y. Li, H. Zhang, R. Murali, B. Li, and M. I. Greene
Human glucocorticoid-induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states
PNAS, April 8, 2008; 105(14): 5465 - 5470.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Liu, Z. Li, S. P. Mahesh, S. Pantanelli, F. S. Hwang, W. O. Siu, and R. B. Nussenblatt
Glucocorticoid-induced Tumor Necrosis Factor Receptor Negatively Regulates Activation of Human Primary Natural Killer (NK) Cells by Blocking Proliferative Signals and Increasing NK Cell Apoptosis
J. Biol. Chem., March 28, 2008; 283(13): 8202 - 8210.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Nagaraju, R. Rawat, E. Veszelovszky, R. Thapliyal, A. Kesari, S. Sparks, N. Raben, P. Plotz, and E. P. Hoffman
Dysferlin Deficiency Enhances Monocyte Phagocytosis: A Model for the Inflammatory Onset of Limb-Girdle Muscular Dystrophy 2B
Am. J. Pathol., March 1, 2008; 172(3): 774 - 785.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. O. Scumpia, M. J. Delano, K. M. Kelly-Scumpia, J. S. Weinstein, J. L. Wynn, R. D. Winfield, C. Xia, C. S. Chung, A. Ayala, M. A. Atkinson, et al.
Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis
Blood, November 15, 2007; 110(10): 3673 - 3681.
[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
 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
 NeuroscientistHome page
O. Aktas, T. Prozorovski, and F. Zipp
Death Ligands and Autoimmune Demyelination
Neuroscientist, August 1, 2006; 12(4): 305 - 316.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
P. E. Fecci, A. E. Sweeney, P. M. Grossi, S. K. Nair, C. A. Learn, D. A. Mitchell, X. Cui, T. J. Cummings, D. D. Bigner, E. Gilboa, et al.
Systemic Anti-CD25 Monoclonal Antibody Administration Safely Enhances Immunity in Murine Glioma without Eliminating Regulatory T Cells.
Clin. Cancer Res., July 15, 2006; 12(14): 4294 - 4305.
[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
 Cancer Res.Home page
A. D. Cohen, A. Diab, M.-A. Perales, J. D. Wolchok, G. Rizzuto, T. Merghoub, D. Huggins, C. Liu, M. J. Turk, N. P. Restifo, et al.
Agonist Anti-GITR Antibody Enhances Vaccine-Induced CD8+ T-Cell Responses and Tumor Immunity.
Cancer Res., May 1, 2006; 66(9): 4904 - 4912.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
O. Saitoh and Y. Nagayama
Regulation of Graves' Hyperthyroidism with Naturally Occurring CD4+CD25+ Regulatory T Cells in a Mouse Model
Endocrinology, May 1, 2006; 147(5): 2417 - 2422.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Kim, W. S. Choi, H. Kang, H. J. Kim, J.-H. Suh, S. Sakaguchi, and B. Kwon
Conversion of Alloantigen-Specific CD8+ T Cell Anergy to CD8+ T Cell Priming through In Vivo Ligation of Glucocorticoid-Induced TNF Receptor
J. Immunol., May 1, 2006; 176(9): 5223 - 5231.
[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. Biol. Chem.Home page
E. M. Esparza, T. Lindsten, J. M. Stockhausen, and R. H. Arch
Tumor Necrosis Factor Receptor (TNFR)-associated Factor 5 Is a Critical Intermediate of Costimulatory Signaling Pathways Triggered by Glucocorticoid-induced TNFR in T Cells
J. Biol. Chem., March 31, 2006; 281(13): 8559 - 8564.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. P. Kohm, J. S. McMahon, J. R. Podojil, W. S. Begolka, M. DeGutes, D. J. Kasprowicz, S. F. Ziegler, and S. D. Miller
Cutting Edge: Anti-CD25 Monoclonal Antibody Injection Results in the Functional Inactivation, Not Depletion, of CD4+CD25+ T Regulatory Cells
J. Immunol., March 15, 2006; 176(6): 3301 - 3305.
[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
 Eur Respir JHome page
A. J. M. van Oosterhout and N. Bloksma
Regulatory T-lymphocytes in asthma
Eur. Respir. J., November 1, 2005; 26(5): 918 - 932.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Suvas, B. Kim, P. P. Sarangi, M. Tone, H. Waldmann, and B. T. Rouse
In Vivo Kinetics of GITR and GITR Ligand Expression and Their Functional Significance in Regulating Viral Immunopathology
J. Virol., September 15, 2005; 79(18): 11935 - 11942.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. J. McGeachy, L. A. Stephens, and S. M. Anderton
Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System
J. Immunol., September 1, 2005; 175(5): 3025 - 3032.
[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
 J. Immunol.Home page
S. A. Quezada, K. Bennett, B. R. Blazar, A. Y. Rudensky, S. Sakaguchi, and R. J. Noelle
Analysis of the Underlying Cellular Mechanisms of Anti-CD154-Induced Graft Tolerance: The Interplay of Clonal Anergy and Immune Regulation
J. Immunol., July 15, 2005; 175(2): 771 - 779.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Bonnefoix, P. Bonnefoix, P. Perron, J.-Q. Mi, W. F. Ng, R. Lechler, J.-C. Bensa, J.-Y. Cahn, and D. Leroux
Quantitating Effector and Regulatory T Lymphocytes in Immune Responses by Limiting Dilution Analysis Modeling
J. Immunol., March 15, 2005; 174(6): 3421 - 3431.
[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
 J. Immunol.Home page
B. T. Rouse and S. Suvas
Regulatory Cells and Infectious Agents: Detentes Cordiale and Contraire
J. Immunol., August 15, 2004; 173(4): 2211 - 2215.
[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 HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.