Essential role of Notch signaling in effector memory CD8+ T cell-mediated airway hyperresponsiveness and inflammation.

ABSTRACT: Adoptive transfer of in vivo-primed CD8(+) T cells or in vitro-generated effector memory CD8(+) T (T(EFF)) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8(-/-)) mice. Examining transcription levels, there was a strong induction of Notch1 in T(EFF) cells compared with central memory CD8(+) T cells. Treatment of T(EFF) cells with a gamma-secretase inhibitor (GSI) strongly inhibited Notch signaling in these cells, and after adoptive transfer, GSI-treated T(EFF) cells failed to restore AHR and airway inflammation in sensitized and challenged recipient CD8(-/-) mice, or to enhance these responses in recipient wild-type (WT) mice. These effects of GSI were also associated with increased expression of the Notch ligand Delta1 in T(EFF) cells. Treatment

SUBMITTER: Okamoto M 

PROVIDER: S-EPMC2373841 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature