HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, P. Articles by Zaghouani, H. Search for Related Content PubMed PubMed Citation Articles by Yu, P. Articles by Zaghouani, H.

Specific T Regulatory Cells Display Broad Suppressive Functions against Experimental Allergic Encephalomyelitis upon Activation with Cognate Antigen¹

Ping Yu^*, Randal K. Gregg^2,*, J. Jeremiah Bell^*, Jason S. Ellis^*, Rohit Divekar^*, Hyun-Hee Lee^*, Renu Jain^*, Hanspeter Waldner^3,, John C. Hardaway^*, Mary Collins, Vijay K. Kuchroo and Habib Zaghouani^4,*

^* Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212; Wyeth Research, Cambridge, MA 02140; and Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

To date, very few Ag-based regimens have been defined that could expand T regulatory (Treg) cells to reverse autoimmunity. Additional understanding of Treg function with respect to specificity and broad suppression should help overcome these limitations. Ig-proteolipid protein (PLP)1, an Ig carrying a PLP1 peptide corresponding to amino acid residues 139-151 of PLP, displayed potent tolerogenic functions and proved effective against experimental allergic encephalomyelitis (EAE). In this study, we took advantage of the Ig-PLP1 system and the PLP1-specific TCR transgenic 5B6 mouse to define a regimen that could expand Ag-specific Treg cells in vivo and tested for effectiveness against autoimmunity involving diverse T cell specificities. The findings indicate that in vivo exposure to aggregated Ig-PLP1 drives PLP1-specific 5B6 TCR transgenic cells to evolve as Treg cells expressing CD25, CTLA-4, and Foxp3 and producing IL-10. These Treg cells were able to suppress PLP1 peptide-induced EAE in both SJL/J and F₁ (SJL/J x C57BL/6) mice. However, despite being effective against disease induced with a CNS homogenate, the Treg cells were unable to counter EAE induced by a myelin basic protein or a myelin oligodendrocyte glycoprotein peptide. Nevertheless, activation with Ag before transfer into the host mice supports suppression of both myelin oligodendrocyte glycoprotein- and myelin basic protein peptide-induced EAE. Thus, it is suggested that activation of Treg cells by the cognate autoantigen is necessary for operation of broad suppressive functions.

Related articles in The JI:

IN THIS ISSUE

The JI 2005 174: 6559-6560. [Full Text]  

This article has been cited by other articles:

				J. Ochoa-Reparaz, A. Rynda, M. A. Ascon, X. Yang, I. Kochetkova, C. Riccardi, G. Callis, T. Trunkle, and D. W. Pascual IL-13 Production by Regulatory T Cells Protects against Experimental Autoimmune Encephalomyelitis Independently of Autoantigen J. Immunol., July 15, 2008; 181(2): 954 - 968. [Abstract] [Full Text] [PDF]

				P. Yu, C. L. Haymaker, R. D. Divekar, J. S. Ellis, J. Hardaway, R. Jain, D. M. Tartar, C. M. Hoeman, J. A. Cascio, A. Ostermeier, et al. Fetal Exposure to High-Avidity TCR Ligand Enhances Expansion of Peripheral T Regulatory Cells J. Immunol., July 1, 2008; 181(1): 73 - 80. [Abstract] [Full Text] [PDF]

				S. Scabeni, M. Lapilla, S. Musio, B. Gallo, E. Ciusani, L. Steinman, R. Mantegazza, and R. Pedotti CD4+CD25+ Regulatory T Cells Specific for a Thymus-Expressed Antigen Prevent the Development of Anaphylaxis to Self J. Immunol., April 1, 2008; 180(7): 4433 - 4440. [Abstract] [Full Text] [PDF]

				G. Tunheim, K. W. Schjetne, I. B. Rasmussen, L. M. Sollid, I. Sandlie, and B. Bogen Recombinant antibodies for delivery of antigen: a single loop between {beta}-strands in the constant region can accommodate long, complex and tandem T cell epitopes Int. Immunol., March 1, 2008; 20(3): 295 - 306. [Abstract] [Full Text] [PDF]

				K. FUJIO, T. OKAMURA, A. OKAMOTO, and K. YAMAMOTO T Cell Receptor Gene Therapy for Autoimmune Diseases Ann. N.Y. Acad. Sci., September 1, 2007; 1110(1): 222 - 232. [Abstract] [Full Text] [PDF]

				N. Kobayashi, H. Kobayashi, L. Gu, T. Malefyt, and T. J. Siahaan Antigen-Specific Suppression of Experimental Autoimmune Encephalomyelitis by a Novel Bifunctional Peptide Inhibitor J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 879 - 886. [Abstract] [Full Text] [PDF]

				R. A. O'Connor, K. H. Malpass, and S. M. Anderton The Inflamed Central Nervous System Drives the Activation and Rapid Proliferation of Foxp3+ Regulatory T Cells J. Immunol., July 15, 2007; 179(2): 958 - 966. [Abstract] [Full Text] [PDF]

				J. Ochoa-Reparaz, C. Riccardi, A. Rynda, S. Jun, G. Callis, and D. W. Pascual Regulatory T Cell Vaccination without Autoantigen Protects against Experimental Autoimmune Encephalomyelitis J. Immunol., February 1, 2007; 178(3): 1791 - 1799. [Abstract] [Full Text] [PDF]

				K. Fujio, A. Okamoto, Y. Araki, H. Shoda, H. Tahara, N. H. Tsuno, K. Takahashi, T. Kitamura, and K. Yamamoto Gene Therapy of Arthritis with TCR Isolated from the Inflamed Paw J. Immunol., December 1, 2006; 177(11): 8140 - 8147. [Abstract] [Full Text] [PDF]

				E. Gonzalez-Rey, A. Fernandez-Martin, A. Chorny, J. Martin, D. Pozo, D. Ganea, and M. Delgado Therapeutic Effect of Vasoactive Intestinal Peptide on Experimental Autoimmune Encephalomyelitis: Down-Regulation of Inflammatory and Autoimmune Responses Am. J. Pathol., April 1, 2006; 168(4): 1179 - 1188. [Abstract] [Full Text] [PDF]

				E. T. Samy, L. A. Parker, C. P. Sharp, and K. S.K. Tung Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node J. Exp. Med., September 19, 2005; 202(6): 771 - 781. [Abstract] [Full Text] [PDF]