Article

Bim is required for T-cell allogeneic responses and graft-versus-host disease in vivo.

American journal of blood research 01/2012; 2(1):77-85. pp.77-85
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
34 Views
  • Article: Lck is required for activation-induced T cell death after TCR ligation with partial agonists.
    Xue-Zhong Yu, Steven D Levin, Joaquin Madrenas, Claudio Anasetti
    [show abstract] [hide abstract]
    ABSTRACT: TCR engagement can induce either T cell proliferation and differentiation or activation-induced T cell death (AICD) through apoptosis. The intracellular signaling pathways that dictate such a disparate fate after TCR engagement have only been partially elucidated. Non-FcR-binding anti-CD3 mAbs induce a partial agonist TCR signaling pattern and cause AICD on Ag-activated, cycling T cells. In this study, we examined TCR signaling during the induction of AICD by anti-CD3 fos, a non-FcR-binding anti-CD3 mAb. This mAb activates Fyn, Lck, and extracellular signal-regulated kinase, and induces phosphorylation of Src-like adapter protein, despite the inability to cause calcium mobilization or TCR polarization. Anti-CD3 fos also fails to effectively activate zeta-associated protein of 70 kDa or NF-kappaB. Using Ag-specific T cells deficient for Fyn or Lck, we provide compelling evidence that activation of Lck is required for the induction of AICD. Our data indicate that a selective and distinct TCR signaling pattern is required for AICD by TCR partial agonist ligands.
    The Journal of Immunology 03/2004; 172(3):1437-43. · 5.79 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

activated T cells
 
allogeneic bone marrow transplantation
 
allogeneic transplantation
 
BH3-only Bcl-2-family protein
 
Bim function
 
CD69 expression
 
donor T cells deficient
 
graft-versus-host disease
 
inflammatory symptoms
 
novel aspect
 
optimal T-cell responses
 
self-antigens
 
studies uncover
 
T cell activation
 
T-cell activation
 
T-cell negative selection
 
T-cell responses
 
TCR engagement
 
thymus
 
viral infections
 

Yu Yu