Fas mediates cardiac allograft acceptance in mice with impaired T-cell-intrinsic NF-κB signaling

被引:2
作者
Molinero, Luciana Lorena [1 ]
Wang, Ying [1 ]
Zhou, Ping
Yagita, Hideo [2 ]
Alegre, Maria-Luisa [1 ]
机构
[1] Univ Chicago, Rheumatol Sect, Dept Med, Chicago, IL 60637 USA
[2] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
关键词
apoptosis; Fas; mouse; NF-kappa B; T cells; tolerance; transplantation; NECROSIS-FACTOR-ALPHA; TRANSPLANTATION TOLERANCE; INDUCED APOPTOSIS; IMMUNE PRIVILEGE; INDUCTION; DEATH; ACTIVATION; REJECTION; LIGAND; EXPRESSION;
D O I
10.1111/j.1432-2277.2009.00875.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
P>The transcription factor NF-kappa B is critical for T-cell activation and survival. We have shown that mice expressing a T-cell-restricted NF-kappa B superrepressor (I kappa B alpha Delta N-Tg) permanently accept heart but not skin allografts. Overexpression of the prosurvival factor Bcl-x(L) in T cells restored heart rejection, suggesting that graft acceptance in I kappa B alpha Delta N-Tg mice was attributable to deletion of alloreactive T cells.In vitro, the increased death of I kappa B alpha Delta N-Tg T cells upon TCR stimulation when compared with wildtype T cells was mostly because of Fas/FasL interaction. Similarly, Fas played a key role in cardiac allograft acceptance by I kappa B alpha Delta N-Tg mice as both genetic and antibody-mediated inhibition of Fas-signaling restored cardiac allograft rejection. Rejection correlated with graft infiltration by T cells and splenic production of IFN-gamma upon allostimulation. These results indicate that T-cell inhibition of NF-kappa B results in cardiac allograft acceptance because of increased susceptibility to Fas-mediated cell death.
引用
收藏
页码:845 / 852
页数:8
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