Role and molecular mechanism of TRAIL transduced rever se signal in T cells
Date Issued
2003
Date
2003
Author(s)
許秉寧
DOI
912320B002192
Abstract
During T cell activation, there are two signals involved to activate the T cells.
One is signal transduced through T cell receptor (TCR), the other is the co-stimulation
signal transduced through CD28 or other co-stimulation molecules. Recently there are
a number of T cell surface molecules with co-stimulation activity reported including
TNF-related apoptosis-inducing ligand (TRAIL, also called Apo2L). TRAIL, a novel
member of TNF superfamily, induces apoptosis in transformed cell lines of diverse
origin. TRAIL is expressed in most of the cells and the expression is upregulated in
activated T cells. The actual biological function of TRAIL/TRAIL receptor is still not
clear. Previous studies in our laboratory, we demonstrated that cross-linking of
TRAIL by plate-bound recombinant TRAIL receptor, DR4-Fc fusion protein
enhanced T cell proliferation and increased IFN-g production in conjunction with
immobilized sub-optimal anti-CD3 stimulation in mouse splenocytes. The increase of
T cell proliferation by DR4-Fc was dose-dependent and this effect could be blocked
by soluble recombinant TRAIL proteins, indicating the occurrence of co-stimulation
effects on T cells via signals transduced through TRAIL (Chou et al., J. Immunol. 167:
1347, 2001). Thus, in addition to its role in inducing apoptosis by binding to the death
receptors, TRAIL itself can enhance T cell proliferation after TCR engagement and
signal the augmentation of IFN-g secretion via a p38-dependent pathway. Our finding
further implied the possibility that TRAIL-induced T cell co-stimulation may be
involved in T cell activation. The significance of TRAIL co-stimulation and other
co-stimulatory molecules in T cell activation is still not clear. Therefore, we further
explore the role of TRAIL co-stimulation on T cells activation and the molecular
mechanism of signal transduction through TRAIL in T cells. We were able to
characterize the T cell subsets responding to TRAIL co-stimulation in T cell
activation and to further investigate role of TRAIL induced co-stimulation in the
pathogenesis of human auotimmune diseases and we demonstrated that TRAIL
costimluate human CD4 T cells and also enhanced the proliferation and IFN-g
production in SLE patients CD4 T cells (manuscripts submitted to Arthritis &
Rheumatism, in revision). For further exploration of the possible molecular
mechanisms of TRAIL-induced T cell co-stimulation, we are studying the possible
signaling pathway and the TRAIL associated molecules in transduction of TRAIL reverse signal as well as other co-stimulation signals in T cell activation by using
proteomics approach for probing the protein kinase activation in signal transduction
during the T cell activation in TRAIL-co-stimulation. We have identified three
possible candidate tyrosine phosphoryated proteins in this approach. This study will
provide a new approach to address the role and molecular mechanisms of TRAIL
induced co-stimulation in T cell activation.
Subjects
TRAIL
reverse signal
human CD4 T cells
tyrosine kinase
SDGs
Publisher
臺北市：國立臺灣大學醫學院免疫學研究所
Type
journal article
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