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Cutting edge: A critical role of B and T lymphocyte attenuator in peripheral T cell tolerance induction


Liu, X; Alexiou, M; Martin-Orozco, N; Chung, Y; Nurieva, R I; Ma, L; Tian, Q; Kollias, G; Lu, S; Graf, D; Dong, C (2009). Cutting edge: A critical role of B and T lymphocyte attenuator in peripheral T cell tolerance induction. Journal of Immunology, 182(8):4516-4520.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Institute of Oral Biology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:April 2009
Deposited On:27 Feb 2010 09:09
Last Modified:05 Apr 2016 14:02
Publisher:American Association of Immunologists
ISSN:0022-1767
Publisher DOI:10.4049/jimmunol.0803161
Official URL:http://www.jimmunol.org/cgi/content/full/182/8/4516
Related URLs:http://www.jimmunol.org/ (Publisher)
PubMed ID:19342624
Permanent URL: http://doi.org/10.5167/uzh-32587

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