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Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

Gebe, John A ; Unrath, Kellee A ; Falk, Ben A ; Kouichi, Ito ; Wen, Li ; Daniels, Terri L ; Lernmark, Åke LU and Nepom, Gerald T (2006) In Clinical Immunology 121(3). p.294-304
Abstract
We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in... (More)
We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes, Tolerance, MHC, T cells, Transgenic
in
Clinical Immunology
volume
121
issue
3
pages
294 - 304
publisher
Elsevier
external identifiers
  • scopus:33750959226
ISSN
1521-6616
DOI
10.1016/j.clim.2006.08.002
language
English
LU publication?
yes
id
5f3b5a9d-d7b1-43a5-a845-9ac2fa301793 (old id 1136259)
date added to LUP
2016-04-01 12:03:05
date last changed
2020-01-12 09:07:05
@article{5f3b5a9d-d7b1-43a5-a845-9ac2fa301793,
  abstract     = {We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice},
  author       = {Gebe, John A and Unrath, Kellee A and Falk, Ben A and Kouichi, Ito and Wen, Li and Daniels, Terri L and Lernmark, Åke and Nepom, Gerald T},
  issn         = {1521-6616},
  language     = {eng},
  number       = {3},
  pages        = {294--304},
  publisher    = {Elsevier},
  series       = {Clinical Immunology},
  title        = {Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.},
  url          = {http://dx.doi.org/10.1016/j.clim.2006.08.002},
  doi          = {10.1016/j.clim.2006.08.002},
  volume       = {121},
  year         = {2006},
}