Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice.
J Exp Med
; 198(5): 809-21, 2003 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-12953096
ABSTRACT
T cell-specific adaptor protein (TSAd) is a T lineage-restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like autoimmune disease. On the nonautoimmune-prone C57BL/6 genetic background, TSAd deficiency results in hypergammaglobulinemia that affects all immunoglobulin (Ig)G subclasses. Older C57BL/6 TSAd-deficient mice (1 yr of age) accumulate large numbers of activated T and B cells in spleen, produce autoantibodies against a variety of self-targets including single stranded (ss) and double stranded (ds) DNA, and, in addition, develop glomerulonephritis. We further show that immunization of younger C57BL/6 TSAd-deficient mice (at age 2 mo) with pristane, a recognized nonspecific inflammatory trigger of lupus, results in more severe glomerulonephritis compared with C57BL/6 controls and the production of high titer ss and ds DNA antibodies of the IgG subclass that are not normally produced by C57BL/6 mice in this model. The development of autoimmunity in TSAd-deficient mice is associated with defective T cell death in vivo. These findings illustrate the role of TSAd as a critical regulator of T cell death whose absence promotes systemic autoimmunity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Carrier Proteins
/
Adaptor Proteins, Signal Transducing
/
Hypergammaglobulinemia
/
Lupus Erythematosus, Systemic
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2003
Document type:
Article
Affiliation country:
United States