Am J Blood Res 2012;2(1):77-85
Original Article
Bim is required for T-cell allogeneic responses and graft-versus-host disease
in vivo
Yu Yu, Jing Yu, Cristina Iclozan, Kane Kaosaard, Claudio Anasetti, Xue-Zhong Yu
Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute,
Tampa, FL 33612, USA; 2Department of Oncologic Sciences; 3Department of Pathology and Cell Biology; University of South
Florida, Tampa, FL, USA.
Received November 5, 2011; accepted November 15, 2011; Epub December 15, 2011; Published December 15, 2011
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 implication 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 PLC1. Our studies uncover a novel aspect of Bim
function in T-cell activation with important implications in understanding of the mechanisms of T-cell activation and tolerance
under allogeneic transplantation. (AJBR11110003).
Keywords: Bim, T cells, proliferation, apoptosis, alloantigen, GVHD, GVL, and BMT
Full Text PDF
Address all correspondence to:
Xue-Zhong Yu, MD
H. Lee Moffitt Cancer Center & Research
Institute, SRB-2,
12902 Magnolia Drive, Tampa, FL 33612-9497
Tel: (813) 745-3562;
Fax: (813) 745-7265;
E-mail:Xue.Yu@moffitt.org
Original Article
Bim is required for T-cell allogeneic responses and graft-versus-host disease
in vivo
Yu Yu, Jing Yu, Cristina Iclozan, Kane Kaosaard, Claudio Anasetti, Xue-Zhong Yu
Departments of Immunology & Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute,
Tampa, FL 33612, USA; 2Department of Oncologic Sciences; 3Department of Pathology and Cell Biology; University of South
Florida, Tampa, FL, USA.
Received November 5, 2011; accepted November 15, 2011; Epub December 15, 2011; Published December 15, 2011
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 implication 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 PLC1. Our studies uncover a novel aspect of Bim
function in T-cell activation with important implications in understanding of the mechanisms of T-cell activation and tolerance
under allogeneic transplantation. (AJBR11110003).
Keywords: Bim, T cells, proliferation, apoptosis, alloantigen, GVHD, GVL, and BMT
Full Text PDF
Address all correspondence to:
Xue-Zhong Yu, MD
H. Lee Moffitt Cancer Center & Research
Institute, SRB-2,
12902 Magnolia Drive, Tampa, FL 33612-9497
Tel: (813) 745-3562;
Fax: (813) 745-7265;
E-mail:Xue.Yu@moffitt.org
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