TRAIL所傳導的逆向訊息在T細胞活化之角色及分子機轉(2/3)
Other Title
Role and molecular mechanism of TRAIL
transduced reverse signal in T cells(2/3)
transduced reverse signal in T cells(2/3)
Date Issued
2004
Date
2004
Author(s)
許秉寧
DOI
922320B002161
Abstract
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-γ 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-γ 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
have characterized 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-γ
production in SLE patients CD4 T cells (Tsai et al. Arthritis & Rheumatism 50:629,
2004). 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 the p38 MAPK and the PI-3K/Akt
pathways were critically involved in TRAIL-induced costimulation of T cells. We also
have identified three possible candidate tyrosine phosphoryated proteins in the 2D gel electrophoresis proteomics 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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