Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection.
Tolerogenic dendritic cells (Tol-DCs) and regulatory T cells (Treg) are key factors in the induction and maintenance of transplantation tolerance. We previously demonstrated that ex vivo-isolated Tol-DCs promote Treg generation, and vice versa, in an in vitro co-culture system. Here we demonstrate the occurrence of such an immune regulatory feedback loop in vivo. Tol-DC generated in vitro by treatment with LF 15-0195 exhibited features of immature DC and express low levels of MHC class II, CD86 and CD40. These Tol-DCs were capable of augmenting CD4(+)CD25(+)CTLA4(+) and FoxP3(+) Treg cell numbers and activity in cardiac allograft recipients. On the other hand, Tol-DCs possessed an ability to generate Treg cells in vitro. The adoptive transfer of these in vitro-generated Treg cells resulted in an increase of Tol-DC in vivo, suggesting that an immune regulatory feedback loop, between Tol-DC and Treg, exists in vivo. Furthermore, the administration of in vitro-generated Tol-DCs or Treg cells prevented rejection of allografts. Co-administration of Tol-DC and Treg synergized efficacy of promoting allograft survival heart transplantation. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro-generated Tol-DCs and Treg.
Zhang
Xusheng
X
Department of Surgery, University of Western Ontario, Canada.
Li
Mu
M
Lian
Dameng
D
Zheng
Xiufen
X
Zhang
Zhu-Xu
ZX
Ichim
Thomas E
TE
Xia
Xiaoping
X
Huang
Xuyan
X
Vladau
Costin
C
Suzuki
Motohiko
M
Garcia
Bertha
B
Jevnikar
Anthony M
AM
Min
Wei-Ping
WP
D019264:Adoptive Transfer; D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival; D006146:Guanidines / Q000494:pharmacology; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*
D051940:B7-2 Antigen; D019013:CD40 Antigens; D006146:Guanidines; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; C434185:LF 150195