Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease.
To understand the relationship between host antigen-presenting cells (APCs) and donor T cells in initiating graft-versus-host disease (GVHD), we followed the fate of host dendritic cells (DCs) in irradiated C57BL/6 (B6) recipient mice and the interaction of these cells with minor histocompatibility antigen- (miHA-) mismatched CD8+ T cells from C3H.SW donors. Host CD11c+ DCs were rapidly activated and aggregated in the T cell areas of the spleen within 6 hours of lethal irradiation. By 5 days after irradiation, <1% of host DCs were detectable, but the activated donor CD8+ T cells had already undergone as many as seven divisions. Thus, proliferation of donor CD8+ T cells preceded the disappearance of host DCs. When C3H.SW donor CD8+ T cells were primed in vivo in irradiated B6 mice or ex vivo by host CD11c+ DCs for 24-36 hours, they were able to proliferate and differentiate into IFN-gamma-producing cells in beta(2)-microglobulin-deficient (beta(2)m(-/-)) B6 recipients and to mediate acute GVHD in beta(2)m(-/-) --> B6 chimeric mice. These results indicate that, although host DCs disappear rapidly after allogeneic bone marrow transplantation, they prime donor T cells before their disappearance and play a critical role in triggering donor CD8+ T cell-mediated GVHD.
Zhang
Yi
Y
Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Louboutin
Jean-Pierre
JP
Zhu
Jiang
J
Rivera
Adam J
AJ
Emerson
Stephen G
SG
D000818:Animals; D017951:Antigen Presentation; D016026:Bone Marrow Transplantation; D018845:CD11 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D018845:CD11 Antigens