Central nervous system destruction mediated by glutamic acid decarboxylase-specific CD4+ T cells.
J Immunol
; 184(9): 4863-70, 2010 May 01.
Article
in En
| MEDLINE
| ID: mdl-20348424
ABSTRACT
High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. In the presence of B cells, high titer anti-GAD65 autoantibodies were generated, but these had no effect on the incidence or severity of disease. In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
Epitopes, T-Lymphocyte
/
Encephalomyelitis
/
Glutamate Decarboxylase
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2010
Type:
Article
Affiliation country:
United States