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

Autoantigens found on pancreatic islets can move to draining lymph nodes, w here they are able to cause the activation and consequent deletion of autor eactive T cells by a mechanism termed cross-tolerance(1,2), This deletion d epends on signalling through CD95 (also known as Fas), a member of the supe rfamily of tumour-necrosis-factor receptors(3). Here we describe a new mech anism that protects against autoimmunity: this mechanism involves another m ember of this superfamily, CD30, whose function was largely unknown. CD30-d eficient islet-specific CD8-positive T cells are roughly 6,000-fold more au toaggressive 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 signa lling, cells activated but not yet deleted by the CD95-dependent cross-tole rance mechanism gain the ability to proliferate extensively upon secondary encounter with antigen on parenchymal tissues, such as the pancreatic islet s. Thus, CD30 signalling limits the proliferative potential of autoreactive CD8 effector T cells and protects the body against autoimmunity.