CD40-CD40 ligand-independent activation of CD8+ T cells can trigger allograft rejection

被引:130
作者
Jones, ND [1 ]
Van Maurik, A [1 ]
Hara, M [1 ]
Spriewald, BM [1 ]
Witzke, O [1 ]
Morris, PJ [1 ]
Wood, KJ [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England
关键词
D O I
10.4049/jimmunol.165.2.1111
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In experimental transplantation, blockade of CD40-CD40 ligand (CD40L) interactions has proved effective at permitting longterm graft survival and has recently been approved for clinical evaluation. We show that CD4(+) T cell-mediated rejection is prevented by anti-CD40L mAb therapy but that CD8(+) T cells remain fully functional. Furthermore, blocking CD40L interactions has no effect on CD8(+) T cell activation, proliferation, differentiation, homing to the target allograft, or cytokine production. We conclude that CD40L is not an important costimulatory molecule for CD8(+) T cell activation and that following transplantation donor APC can activate recipient CD8(+) T cells directly without first being primed by CD4(+) T cells.
引用
收藏
页码:1111 / 1118
页数:8
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