The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes.

ABSTRACT: The critical role of CTLA-4 in inhibiting Ag-driven T cell responses upon engagement with its ligands, B7-1 and B7-2 and its importance for peripheral T cell tolerance and T cell homeostasis has been studied intensively. The CTLA-4 splice variant ligand-independent (li)-CTLA-4 is expressed in naive and activated T cells and can actively alter T cell signaling despite its lack of a B7 binding domain. To study the effect of li-CTLA-4 in regulating T cell responses in the context of autoimmunity, we engineered a B6.CTLA-4 (floxed-Exon2)-BAC-transgene, resulting in selective expression of li-CTLA-4 upon Cre-mediated deletion of Exon 2. Introducing the B6.BAC into the NOD background, which is genetically deficient for li-CTLA-4, restores mRNA levels of li-CTLA-4 to those observed in C57BL/6 mic

SUBMITTER: Stumpf M 

PROVIDER: S-EPMC3568535 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature