Cutting edge: A critical role of B and T lymphocyte attenuator in peripheral T cell tolerance induction.
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.
Liu
Xikui
X
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Alexiou
Maria
M
Martin-Orozco
Natalia
N
Chung
Yeonseok
Y
Nurieva
Roza I
RI
Ma
Li
L
Tian
Qiang
Q
Kollias
George
G
Lu
Sijie
S
Graf
Daniel
D
Dong
Chen
C