TY - JOUR
T1 - Reduced Graft-versus-Host Disease in C3-Deficient Mice Is Associated with Decreased Donor Th1/Th17 Differentiation
AU - Ma, Qing
AU - Li, Dan
AU - Nurieva, Roza
AU - Patenia, Rebecca
AU - Bassett, Roland
AU - Cao, Wei
AU - Alekseev, Andrei M.
AU - He, Hong
AU - Molldrem, Jeffrey J.
AU - Kroll, Michael H.
AU - Champlin, Richard E.
AU - Sale, George E.
AU - Afshar-Kharghan, Vahid
N1 - Funding Information:
Financial disclosure: This work was supported in part by American Cancer Society grant RSG-08-183-01-LIB (to Qing Ma), National Institutes of Health/National Institute of Allergy and Infectious Diseases grant 5-R01-AI081761 (to Roza Nurieva), and Cancer Prevention & Research Institute of Texas grant RP101374 (to Vahid Afshar-Kharghan). The authors have no conflicts of interest to disclose.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Alloimmune responses
KW - Dendritic cell
KW - T lymphocyte
KW - The complement system
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U2 - 10.1016/j.bbmt.2012.05.014
DO - 10.1016/j.bbmt.2012.05.014
M3 - Article
C2 - 22664751
AN - SCOPUS:84864022365
SN - 1083-8791
VL - 18
SP - 1174
EP - 1181
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -