Neonatal tumor necrosis factor α promotes diabetes in nonobese diabetic mice by CD154-independent antigen presentation to CD8+ T cells

被引:61
作者
Green, EA
Wong, FS
Eshima, K
Mora, C
Flavell, RA
机构
[1] Yale Univ, Sch Med, Immunol Sect, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
关键词
TNF-alpha; CD154; diabetes; NOD mice; CD8(+) cells;
D O I
10.1084/jem.191.2.225
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Neonatal islet-specific expression of tumor necrosis factor (TNF)-alpha in nonobese diabetic mice promotes diabetes by provoking islet-infiltrating antigen-presenting cells to present islet peptides to autoreactive T cells. Here we show that TNF-alpha promotes autoaggression of both effector CD4(+) and CD8(+) T cells. Whereas CD8(+) T cells are critical for diabetes progression, CD4(+) T cells play a lesser role. TNF-alpha-mediated diabetes development was not dependent on CD154-CD40 signals or activated CD4(+) T cells. Instead, it appears that TNF-alpha can promote cross-presentation of islet antigen to CD8(+) T cells using a unique CD40-CD154-independent pathway. These data provide new insights into the mechanisms by which inflammatory stimuli call bypass CD151-CD40 immune regulatory signals and cause activation of autoreactive T cells.
引用
收藏
页码:225 / 237
页数:13
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