Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE)

doi:10.1084/jem.184.5.1609

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Kumar, V.
	Articles by Sercarz, E.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Kumar, V.
	Articles by Sercarz, E.


Social Bookmarking

	What's this?

ARTICLES

Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE)

V Kumar, K Stellrecht and E Sercarz
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095-1489.

T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1- 9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide- specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

De Sarno, P., Axtell, R. C., Raman, C., Roth, K. A., Alessi, D. R., Jope, R. S. (2008). Lithium Prevents and Ameliorates Experimental Autoimmune Encephalomyelitis. J. Immunol. 181: 338-345 [Abstract] [Full Text]
Madakamutil, L. T., Maricic, I., Sercarz, E. E., Kumar, V. (2008). Immunodominance in the TCR Repertoire of {alpha}TCR Peptide-Specific CD4+ Treg Population That Controls Experimental Autoimmune Encephalomyelitis. J. Immunol. 180: 4577-4585 [Abstract] [Full Text]
Turner, M. S., Cohen, P. A., Finn, O. J. (2007). Lack of Effective MUC1 Tumor Antigen-Specific Immunity in MUC1-Transgenic Mice Results from a Th/T Regulatory Cell Imbalance That Can Be Corrected by Adoptive Transfer of Wild-Type Th Cells. J. Immunol. 178: 2787-2793 [Abstract] [Full Text]
Luo, Y., Wen, Y.-J., Ding, Z.-Y., Fu, C.-H., Wu, Y., Liu, J.-Y., Li, Q., He, Q.-M., Zhao, X., Jiang, Y., Li, J., Deng, H.-X., Kang, B., Mao, Y.-Q., Wei, Y.-Q. (2006). Immunotherapy of tumors with protein vaccine based on chicken homologous tie-2.. Clin. Cancer Res. 12: 1813-1819 [Abstract] [Full Text]
Liu, J.-y., Wei, Y.-q., Yang, L., Zhao, X., Tian, L., Hou, J.-m., Niu, T., Liu, F., Jiang, Y., Hu, B., Wu, Y., Su, J.-m., Lou, Y.-y., He, Q.-m., Wen, Y.-j., Yang, J.-l., Kan, B., Mao, Y.-q., Luo, F., Peng, F. (2003). Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2. Blood 102: 1815-1823 [Abstract] [Full Text]
He, Q.-m., Wei, Y.-q., Tian, L., Zhao, X., Su, J.-m., Yang, L., Lu, Y., Kan, B., Lou, Y.-y., Huang, M.-j., Xiao, F., Liu, J.-y., Hu, B., Luo, F., Jiang, Y., Wen, Y.-j., Deng, H.-x., Li, J., Niu, T., Yang, J.-l. (2003). Inhibition of Tumor Growth with a Vaccine Based on Xenogeneic Homologous Fibroblast Growth Factor Receptor-1 in Mice. J. Biol. Chem. 278: 21831-21836 [Abstract] [Full Text]
Madakamutil, L. T., Maricic, I., Sercarz, E., Kumar, V. (2003). Regulatory T Cells Control Autoimmunity In Vivo by Inducing Apoptotic Depletion of Activated Pathogenic Lymphocytes. J. Immunol. 170: 2985-2992 [Abstract] [Full Text]
Lu, Y., Wei, Y.-q., Tian, L., Zhao, X., Yang, L., Hu, B., Kan, B., Wen, Y.-j., Liu, F., Deng, H.-x., Li, J., Mao, Y.-q., Lei, S., Huang, M.-j., Peng, F., Jiang, Y., Zhou, H., Zhou, L.-q., Luo, F. (2003). Immunogene Therapy of Tumors with Vaccine Based on Xenogeneic Epidermal Growth Factor Receptor. J. Immunol. 170: 3162-3170 [Abstract] [Full Text]
Su, J.-M., Wei, Y.-Q., Tian, L., Zhao, X., Yang, L., He, Q.-M., Wang, Y., Lu, Y., Wu, Y., Liu, F., Liu, J.-Y., Yang, J.-L., Lou, Y.-Y., Hu, B., Niu, T., Wen, Y.-J., Xiao, F., Deng, H.-X., Li, J., Kan, B. (2003). Active Immunogene Therapy of Cancer with Vaccine On the Basis of Chicken Homologous Matrix Metalloproteinase-2. Cancer Res. 63: 600-607 [Abstract] [Full Text]
Braciak, T. A., Pedersen, B., Chin, J., Hsiao, C., Ward, E. S., Maricic, I., Jahng, A., Graham, F. L., Gauldie, J., Sercarz, E. E., Kumar, V. (2003). Protection Against Experimental Autoimmune Encephalomyelitis Generated by a Recombinant Adenovirus Vector Expressing the V{beta}8.2 TCR Is Disrupted by Coadministration with Vectors Expressing Either IL-4 or -10. J. Immunol. 170: 765-774 [Abstract] [Full Text]
Zelenika, D., Adams, E., Humm, S., Graca, L., Thompson, S., Cobbold, S. P., Waldmann, H. (2002). Regulatory T Cells Overexpress a Subset of Th2 Gene Transcripts. J. Immunol. 168: 1069-1079 [Abstract] [Full Text]
Jahng, A. W., Maricic, I., Pedersen, B., Burdin, N., Naidenko, O., Kronenberg, M., Koezuka, Y., Kumar, V. (2001). Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis. J. Exp. Med. 194: 1789-1799 [Abstract] [Full Text]
Li, J., Goldstein, I., Glickman-Nir, E., Jiang, H., Chess, L. (2001). Induction of TCR V{beta}-Specific CD8+ CTLs by TCR V{beta}-Derived Peptides Bound to HLA-E. J. Immunol. 167: 3800-3808 [Abstract] [Full Text]
Wei, Y.-q., Huang, M.-j., Yang, L., Zhao, X., Tian, L., Lu, Y., Shu, J.-m., Lu, C.-j., Niu, T., Kang, B., Mao, Y.-q., Liu, F., Wen, Y.-j., Lei, S., Luo, F., Zhou, L.-q., Peng, F., Jiang, Y., Liu, J.-y., Zhou, H., Wang, Q.-r., He, Q.-m., Xiao, F., Lou, Y.-y., Xie, X.-j., Li, Q., Wu, Y., Ding, Z.-y., Hu, B., Hu, M., Zhang, W. (2001). Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen. Proc. Natl. Acad. Sci. USA 10.1073/pnas.191112198v1 [Abstract] [Full Text]
Kumar, V., Maglione, J., Thatte, J., Pederson, B., Sercarz, E., Ward, E. S. (2001). Induction of a type 1 regulatory CD4 T cell response following V{beta}8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis. Int Immunol 13: 835-841 [Abstract] [Full Text]
van Tienhoven, E. A. E., Broeren, C. P. M., Noordzij, A., Wagenaar, J. P. A., van Eden, W., Wauben, M. H. M. (2000). Nasal application of a naturally processed and presented T cell epitope derived from TCR AV11 protects against adjuvant arthritis. Int Immunol 12: 1715-1721 [Abstract] [Full Text]
Wan, Y., Bramson, J., Pilon, A., Zhu, Q., Gauldie, J. (2000). Genetically Modified Dendritic Cells Prime Autoreactive T Cells through a Pathway Independent of CD40L and Interleukin 12: Implications for Cancer Vaccines. Cancer Res. 60: 3247-3253 [Abstract] [Full Text]
Olivares-Villagomez, D., Wensky, A. K., Wang, Y., Lafaille, J. J. (2000). Repertoire Requirements of CD4+ T Cells That Prevent Spontaneous Autoimmune Encephalomyelitis. J. Immunol. 164: 5499-5507 [Abstract] [Full Text]
Overwijk, W. W., Lee, D. S., Surman, D. R., Irvine, K. R., Touloukian, C. E., Chan, C.-C., Carroll, M. W., Moss, B., Rosenberg, S. A., Restifo, N. P. (1999). Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: Requirement for CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 96: 2982-2987 [Abstract] [Full Text]
Kumar, V., Sercarz, E. (1998). Induction or Protection from Experimental Autoimmune Encephalomyelitis Depends on the Cytokine Secretion Profile of TCR Peptide-Specific Regulatory CD4 T Cells. J. Immunol. 161: 6585-6591 [Abstract] [Full Text]
Olivares-Villagomez, D., Wang, Y., Lafaille, J. J. (1998). Regulatory CD4+ T Cells Expressing Endogenous T Cell Receptor Chains Protect Myelin Basic Protein-specific Transgenic Mice from Spontaneous Autoimmune Encephalomyelitis. J. Exp. Med. 188: 1883-1894 [Abstract] [Full Text]
Borghans, J. A. M., De Boer, R. J., Sercarz, E., Kumar, V. (1998). T Cell Vaccination in Experimental Autoimmune Encephalomyelitis: A Mathematical Model. J. Immunol. 161: 1087-1093 [Abstract] [Full Text]
Luhder, F., Katz, J., Benoist, C., Mathis, D. (1998). Major Histocompatibility Complex Class II Molecules Can Protect from Diabetes by Positively Selecting T Cells with Additional Specificities. J. Exp. Med. 187: 379-387 [Abstract] [Full Text]
Kumar, V., Aziz, F., Sercarz, E., Miller, A. (1997). Regulatory T Cells Specific for the Same Framework 3�Region of the Vbeta 8.2 Chain Are Involved in the Control of Collagen II-induced Arthritis and Experimental Autoimmune Encephalomyelitis. J. Exp. Med. 185: 1725-1733 [Abstract] [Full Text]
Wei, Y.-q., Huang, M.-j., Yang, L., Zhao, X., Tian, L., Lu, Y., Shu, J.-m., Lu, C.-j., Niu, T., Kang, B., Mao, Y.-q., Liu, F., Wen, Y.-j., Lei, S., Luo, F., Zhou, L.-q., Peng, F., Jiang, Y., Liu, J.-y., Zhou, H., Wang, Q.-r., He, Q.-m., Xiao, F., Lou, Y.-y., Xie, X.-j., Li, Q., Wu, Y., Ding, Z.-y., Hu, B., Hu, M., Zhang, W. (2001). Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen. Proc. Natl. Acad. Sci. USA 98: 11545-11550 [Abstract] [Full Text]