Targeted deletion of CD44v7 exon leads to decreased endothelial cell injury but not @entity5 cell killing mediated by XXXX -activated cytolytic lymphocytes.

@entity137 @entity455 @entity2047 @entity5 @entity19 @entity4357 @entity669 @entity3844
In the current study, we investigated the nature and role of @entity3844 variant isoforms involved in endothelial cell (EC) @entity5 cell @entity137 mediated by @entity2047 -activated killer (LAK) cells. Treatment of @entity3844 wild-type lymphocytes with @entity2047 led to increased gene expression of @entity3844 v6 and v7 variant isoforms and to significant induction of @entity455 ( @entity455 ). CD44v6-v7 knockout (KO) and CD44v7 KO @entity19 showed markedly reduced levels of @entity2047 -induced @entity455 . The decreased @entity455 in CD44v6-v7 KO and CD44v7 KO @entity19 did not result from differential activation and expansion of CD8+ T cells, NK, and NK-T cells or from altered degree of perivascular lymphocytic infiltration in the lungs. LAK cells from CD44v7 KO @entity19 showed a significant decrease in their ability to adhere to and mediate lysis of EC but not lysis of @entity19 @entity5 cells in vitro. CD44v7-mediated lysis of EC by LAK cells was dependent on the activity of @entity4357 3-kinase and @entity669 kinases. Interestingly, @entity2047 -activated LAK cells expressing @entity3844 hi but not @entity3844 lo were responsible for EC lysis. Furthermore, lysis of EC targets could be blocked by addition of soluble or enzymatic cleavage of CD44v6-v7-binding glycosaminoglycans. Finally, anti-CD44v7 mAbs caused a significant reduction in the adherence to and killing of EC and led to suppression of @entity2047 -induced @entity455 . Together, this study suggests that the expression of CD44v7 on LAK cells plays a specific role in EC injury and that it may be possible to reduce EC injury but not @entity5 cell killing by specifically targeting CD44v7.
