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 Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liu, X. Articles by Dong, C. Search for Related Content PubMed PubMed Citation Articles by Liu, X. Articles by Dong, C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene

Cutting Edge: A Critical Role of B and T Lymphocyte Attenuator in Peripheral T Cell Tolerance Induction ¹

Xikui Liu^*, Maria Alexiou, Natalia Martin-Orozco^*, Yeonseok Chung^*, Roza I. Nurieva^*, Li Ma, Qiang Tian, George Kollias, Sijie Lu, Daniel Graf^2, and Chen Dong^2,*

^* Department of Immunology and Department of Stem Cell Transplantation and Cellular Therapy, M. D. Anderson Cancer Center, Houston, TX 77030; Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming," Vari, Greece; and Institute for Systems Biology, Seattle, WA 98103

T cell activation and tolerance are delicately regulated by costimulatory molecules. Although B and T lymphocyte attenuator (BTLA) has been shown as a negative regulator for T cell activation, its role in peripheral T cell tolerance induction in vivo has not been addressed. In this study, we generated a novel strain of BTLA-deficient mice and used three different models to characterize the function of BTLA in controlling T cell tolerance. In an oral tolerance model, BTLA-deficient mice were found resistant to the induction of T cell tolerance to an oral Ag. Moreover, compared with wild-type OT-II cells, BTLA^–/– OT-II cells were less susceptible to tolerance induction by a high-dose OVA peptide administered i.v. Finally, BTLA^–/– OT-I cells caused autoimmune diabetes in RIP-mOVA recipient mice. Our results thus demonstrate an important role for BTLA in the induction of peripheral tolerance of both CD4⁺ and CD8⁺ T cells in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported in part by National Institutes of Health Grant AI054912 (to C.D.), a Specialized Center of Research sub-grant from the Leukemia and Lymphoma Society (to C.D.), and a grant from the Center for Target Therapy of M. D. Anderson Cancer Center (to C.D.). D.G. was a recipient of a Marie Curie fellowship, and D.G., G.K., and M.A. received support from MUGEN Network of Excellence 6FP (LSHG-CT-2005-005203). X.L. received a postdoctoral fellowship from the Arthritis Foundation, R.I.N. received an American Heart Association Scientist Development award, and C.D. received a Cancer Research Institute Investigator award, an American Lung Association Career Investigator award, a Leukemia and Lymphoma Society Scholar award, and a Trust Fellowship of the M. D. Anderson Cancer Center.

² Address correspondence and reprint requests to Dr. Chen Dong, Department of Immunology, M. D. Anderson Cancer Center, 7455 Fannin Street, Unit 902, Houston, TX 77030. E-mail address: cdong{at}mdanderson.org or Dr. Daniel Graf, Institute of Immunology, Biomedical Sciences Research Center ‘Alexander Fleming,’ 34 Al. Fleming Street, 166 72 Vari, Hellas/Greece. E-mail address: graf{at}fleming.gr

³ Abbreviations used in this paper: BTLA, B and T lymphocyte attenuator; HVEM, herpesvirus entry mediator; KO, knockout; mOVA, membrane-bound OVA; PLN, pancreatic lymph node; RIP, rat insulin promoter; WT, wild type.