Tolerogenic dendritic cells transferring hyporesponsiveness and synergizing T regulatory cells in transplant tolerance.
Dendritic cells are among the most potent antigen-presenting cells and are important in the development of both immunity and tolerance. Tolerogenic dendritic cell (Tol-DC) is a key factor in the induction and maintenance of tolerance during transplantation. However, the precise mechanism and direct evidence of in vivo immune modulation remain unclear. In the present study, we identified critical roles of immune modulation on transplant tolerance through interactions between Tol-DCs and regulatory T (Treg) cells. Tol-DCs remained in an immature state and were insensitive to maturation stimuli. Tol-DCs in tolerant recipients heightened the expression of indoleamine 2,3-dioxygenase (IDO) that induced allogeneic T-cell apoptosis. Adoptive transfer of Tol-DCs isolated from primary tolerant recipients resulted in augmentation of CD4(+)CD25(+)CTLA4(+) Treg cells and prolonged graft survival in secondary allogeneic heart transplantation and synergized with Treg cells to induce tolerance in secondary recipients. This study indicates that Tol-DC offers two functions during the process of tolerogenesis: suppression of anti-donor T-cell responses through production of IDO and interaction with Treg cells, which provides a framework for future research into tolerance induction.
Li
Mu
M
Department of Surgery, University of Western Ontario, London, Ontario, Canada.
Zhang
Xusheng
X
Zheng
Xiufen
X
Lian
Dameng
D
Zhang
Zhu-Xu
ZX
Sun
Hongtao
H
Suzuki
Motohiko
M
Vladau
Costin
C
Huang
Xuyan
X
Xia
Xiaoping
X
Zhong
Robert
R
Garcia
Bertha
B
Min
Wei-Ping
WP
D019264:Adoptive Transfer; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D004357:Drug Synergism; D016027:Heart Transplantation; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D015854:Up-Regulation
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase