RGD Reference Report - Induction of autoimmunity in the absence of CD28 costimulation. - Chinchilla Research Resource Database
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Induction of autoimmunity in the absence of CD28 costimulation.

Authors: Bachmaier, K  Pummerer, C  Shahinian, A  Ionescu, J  Neu, N  Mak, T W  Penninger, J M 
Citation: Bachmaier K, etal., J Immunol. 1996 Aug 15;157(4):1752-7.
CRRD ID: 13702883
Pubmed: (View Article at PubMed) PMID:8759765

Ag-specific activation of T lymphocytes requires two signals, one by the TCR and a second by costimulatory molecules. In a CD4+ T helper cell-dependent experimental autoimmune myocarditis model, we provide genetic evidence that cardiac myosin-induced autoimmune myocarditis and the production of IgG auto-Abs is dependent on functional T cells and did not occur in mice lacking the tyrosine kinase p56lck or the tyrosine phosphatase CD45. By contrast, animals lacking the T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease, although at significantly lower severity than in heterozygous littermates, and produced IgG auto-Abs depending on the concentration of the autoantigen administered. In addition, the isotypes of IgG auto-Abs specific for cardiac myosin differed between CD28 +/- and CD28 -/- mice. Whereas CD28 +/- mice predominantly produced Th2-mediated IgG1 auto-Abs, CD28 -/- mice produced predominantly IgG2a. These data suggest that CD28 costimulation plays a crucial role in induction and maintenance of autoimmune heart disease and that CD28 expression is required for predominant Th2-IgG1 responses in an autoimmune setting.

Annotation

Disease Annotations    

Objects Annotated

Genes (Homo sapiens)
CD28  (CD28 molecule)


Additional Information

 



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