Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells

被引:102
作者
Kurts, C
Carbone, FR
Krummel, MF
Koch, KM
Miller, JFAP
Heath, WR [1 ]
机构
[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3050, Australia
[2] Monash Med Sch, Dept Pathol & Immunol, Prahran, Vic 3181, Australia
[3] Med Hsch Hannover, Dept Nephrol, D-30625 Hannover, Germany
关键词
D O I
10.1038/18692
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Autoantigens found on pancreatic islets can move to draining lymph nodes, where they are able to cause the activation and consequent deletion of autoreactive T cells by a mechanism termed cross-tolerance(1,2), This deletion depends on signalling through CD95 (also known as Fas), a member of the superfamily of tumour-necrosis-factor receptors(3). Here we describe a new mechanism that protects against autoimmunity: this mechanism involves another member of this superfamily, CD30, whose function was largely unknown. CD30-deficient islet-specific CD8-positive T cells are roughly 6,000-fold more autoaggressive than wild-type cells, with the transfer of as few as 160 CD30-deficient T cells leading to the complete destruction of pancreatic islets and the rapid onset of diabetes. We show that, in the absence of CD30 signalling, cells activated but not yet deleted by the CD95-dependent cross-tolerance mechanism gain the ability to proliferate extensively upon secondary encounter with antigen on parenchymal tissues, such as the pancreatic islets. Thus, CD30 signalling limits the proliferative potential of autoreactive CD8 effector T cells and protects the body against autoimmunity.
引用
收藏
页码:341 / 344
页数:4
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