Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells.
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. This deletion depends on signalling through CD95 (also known as Fas), a member of the superfamily of tumour-necrosis-factor receptors. 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.
Kurts
C
C
The Department of Nephrology, Medizinische Hochschule, Hannover, Germany.
Carbone
F R
FR
Krummel
M F
MF
Koch
K M
KM
Miller
J F
JF
Heath
W R
WR
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D017637:Clonal Deletion; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000276:immunology; D017730:Ki-1 Antigen / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction; D018183:Transplantation Chimera
D017730:Ki-1 Antigen; D010047:Ovalbumin