Reduced graft-versus-host disease in C3-deficient mice is associated with decreased donor Th1/Th17 differentiation.
Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation is mediated by the activation of recipient dendritic cells and subsequent proliferation of donor T cells. The complement system was recently shown to modulate adaptive immunity through an interaction of the complement system and lymphocytes. Complement proteins participate in the activation of dendritic cells, antigen presentation to T cells, and proliferation of T cells. Our studies with a murine model of bone marrow transplantation demonstrate that complement system regulates alloimmune responses in GVHD. Mice deficient in the central component of the complement system (C3(-/-)) had significantly lower GVHD-related mortality and morbidity compared with wild-type recipient mice. The numbers of donor-derived T cells, including IFN-γ(+), IL-17(+), and IL-17(+)IFN-γ(+) subsets, were decreased in secondary lymphoid organs of C3(-/-) recipients. Furthermore, the number of recipient CD8α(+)CD11c(+) cells in lymphoid organs was reduced. We conclude that C3 regulates Th1/17 differentiation in bone marrow transplantation, and define a novel function of the complement system in GVHD.
Section of Transplantation Immunology, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Qing
Q
Ma
Dan
D
Li
Roza
R
Nurieva
Rebecca
R
Patenia
Roland
R
Bassett
Wei
W
Cao
Andrei M
AM
Alekseev
Hong
H
He
Jeffrey J
JJ
Molldrem
Michael H
MH
Kroll
Richard E
RE
Champlin
George E
GE
Sale
Vahid
V
Afshar-Kharghan
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency* / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D003176:Complement C3