PMID- 10192335
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20171116
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6725
DP  - 1999 Mar 25
TI  - Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T
      cells.
PG  - 341-4
AB  - 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.
FAU - Kurts, C
AU  - Kurts C
AD  - The Department of Nephrology, Medizinische Hochschule, Hannover, Germany.
FAU - Carbone, F R
AU  - Carbone FR
FAU - Krummel, M F
AU  - Krummel MF
FAU - Koch, K M
AU  - Koch KM
FAU - Miller, J F
AU  - Miller JF
FAU - Heath, W R
AU  - Heath WR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Ki-1 Antigen)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
SB  - X
EIN - Nature 2000 Sep 21;407(6802):413
MH  - Adoptive Transfer
MH  - Animals
MH  - Autoimmunity
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism/transplantation
MH  - Clonal Deletion
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Immune Tolerance
MH  - Islets of Langerhans/immunology
MH  - Ki-1 Antigen/*metabolism
MH  - Lymph Nodes/immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Ovalbumin/immunology
MH  - *Signal Transduction
MH  - Transplantation Chimera
EDAT- 1999/04/07 02:01
MHDA- 2001/03/23 10:01
CRDT- 1999/04/07 02:01
PHST- 1999/04/07 02:01 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/07 02:01 [entrez]
AID - 10.1038/18692 [doi]
PST - ppublish
SO  - Nature. 1999 Mar 25;398(6725):341-4. doi: 10.1038/18692.