Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4(+)CD25(+) regulatory T cells.
CD4(+)CD25(+) regulatory T cells (Treg) are potent immunosuppressive cells active in controlling normal pathological immune responses. The mechanisms of this suppression have been investigated under various conditions. In this report, tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/death receptor 5 (DR5) was explored as one of the pivotal factors for the suppression and cytotoxicity induced by CD4(+)CD25(+) Treg. Cell death was involved in the suppression induced by activated CD4(+)CD25(+) Treg in vitro. The induction of CD4(+) T cell death was not mediated by the CD95/CD95L pathway, but rather depended upon the upregulation of TRAIL in the Treg. Blocking the TRAIL/DR5 pathway resulted in a significant reduction of the suppressive activity as well as the cytotoxic effects of Treg in vitro. Activated Treg displayed TRAIL-dependent cytotoxicity against CD4(+) T cells in vivo. The prolonged survival of allogeneic skin grafts induced by Treg was inhibited by DR5-blocking antibodies. Our findings suggest that the TRAIL/DR5 pathway is one of the mechanisms used by Treg to regulate immune responses both in vitro and in vivo.
Ren
X
X
Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, China.
Ye
F
F
Jiang
Z
Z
Chu
Y
Y
Xiong
S
S
Wang
Y
Y
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D019138:Antibodies, Blocking; D053645:Interleukin-2 Receptor alpha Subunit; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor