title: Bim is required for T-cell allogeneic responses and graft-versus-host disease in vivo.
abstract: Bim, a BH3-only Bcl-2-family protein, is essential for T-cell negative selection in the thymus as well as for the death of activated T cells in the periphery. The role of Bim has been extensively studied in T-cell responses to self-antigens and viral infections. Recent findings on Bim in autoimmunity triggered our interest in investigating whether Bim may play a role in another disease with inflammatory symptoms as graft-versus-host disease (GVHD). Here we report that Bim is required for optimal T-cell responses to alloantigens in vivo and for the development of GVHD. Using murine models of allogeneic bone marrow transplantation (BMT), we found that donor T cells deficient for Bim are impaired in the induction of GVHD primarily due to a significant defect in T cell activation and expansion in vivo. Upon TCR engagement, Bim(-/-) T cells exhibited selective defects in CD69 expression and phosphorylation of PLCγ1. Our studies uncover a novel aspect of Bim function in T-cell activation with important implications in understanding the mechanisms of T-cell activation and tolerance under allogeneic transplantation.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Cristina
authors.initials: C
authors.lastname: Iclozan
authors.forename: Kane
authors.initials: K
authors.lastname: Kaosaard
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu