[HTML][HTML] Reduced graft-versus-host disease in C3-deficient mice is associated with decreased donor Th1/Th17 differentiation

Q Ma, D Li, R Nurieva, R Patenia, R Bassett… - Biology of Blood and …, 2012 - Elsevier
Q Ma, D Li, R Nurieva, R Patenia, R Bassett, W Cao, AM Alekseev, H He, JJ Molldrem…
Biology of Blood and Marrow Transplantation, 2012Elsevier
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 …
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.
Elsevier