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Production in T Cells by Signal Transduced Through TNF-Related Apoptosis-Inducing Ligand1
*
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China;
Department of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China; and
Department of Internal Medicine, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan, Republic of China
TNF-related apoptosis-inducing ligand (TRAIL, also called Apo2L), 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 up-regulated in activated T cells. Four receptors for
TRAIL have been identified, and there is complex interplay between
TRAIL and TRAIL receptors in vivo. The actual biological function of
TRAIL/TRAIL receptor is still not clear. Growing evidence has
demonstrated that members of TNF superfamily transduce signals after
engagement with their receptors. Cross-linking of TRAIL by plate-bound
rTRAIL receptor, death receptor 4-Fc fusion protein enhanced T cell
proliferation and increased IFN-
production in conjunction with
immobilized suboptimal anti-CD3 stimulation in mouse splenocytes.
The increase of T cell proliferation by death receptor 4-Fc was dose
dependent, and this effect could be blocked by soluble rTRAIL proteins,
indicating the occurrence of reverse signaling through TRAIL on T cell.
The enhanced secretion of IFN- mediated via TRAIL could be blocked
by SB203580, a p38 mitogen-activated protein kinase-specific inhibitor.
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- secretion via a
p38-dependent pathway. This provides another example of reverse
signaling by a member of TNF superfamily. In conclusion, our data
suggest that TRAIL can itself transduce a reverse signal, and this may
shed light on the biological function of TRAIL.
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