CTLA4-Ig inhibits allergic airway inflammation by a novel CD28-independent, nitric oxide synthase-dependent mechanism.

ABSTRACT: The T-cell response to antigen depends upon coordinate signaling between costimulatory and inhibitory receptors. Altered function of either may underlie the pathophysiology of autoimmune and/or chronic inflammatory diseases and manipulation of these pathways is an important emerging area of therapeutics. We report here that the immunosuppressant drug CTLA4-Ig inhibits the effector phase of allergic airway inflammation through a CD28-independent, nitric oxide synthase dependent mechanism. Using mice deficient in both B and T lymphocyte attenuator (BTLA) and CD28, we demonstrate that simultaneous deficiency of an inhibitory receptor can rescue the in vivo but not the in vitro CD28-deficient phenotype. Furthermore, we demonstrate that inflammation in the CD28/BTLA-double-deficient mice is sup

SUBMITTER: Deppong CM 

PROVIDER: S-EPMC3039706 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature