A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells that promotes skin allograft survival in mice.
Semimature dendritic cells (smDCs) can induce autoimmune tolerance by activation of host antigen-specific CD4(+)CD25(+) regulatory T (Treg) cells. We hypothesized that donor smDCs injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4(+)CD25(+)Treg cells, and promote skin allograft survival. Myeloid smDCs were derived from C57BL/6J mice (donors) in vitro. BALB/c mice (recipients) were injected with smDCs to generate antigen-specific CD4(+)CD25(+)Treg cells in vivo. Allograft survival was prolonged when BALB/c recipients received either C57BL/6J smDCs prior to grafting or C57BL/6J smDC-derived CD4(+)CD25(+)Treg cells post-grafting, and skin flaps from these grafts showed the highest IL-10 production regardless of rapamycin treatments. Our findings confirm that smDCs constitute an independent subgroup of DCs that play a key role for inducing CD4(+)CD25(+)Treg cells to express high IL-10 levels, which induce hyporesponsiveness of effector T cells. Pre-treating recipients with donor smDCs may have potential for transplant tolerance induction.
Fu
Bi-mang
BM
Department of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guang Zhou, China.
He
Xiao-shun
XS
Yu
Si
S
Hu
An-bin
AB
Zhang
Jie
J
Ma
Yi
Y
Tam
Nga-lei
NL
Huang
Jie-fu
JF
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006085:Graft Survival; D006967:Hypersensitivity / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012867:Skin / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D053645:Interleukin-2 Receptor alpha Subunit