Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease.
Alloantigen expression on host APCs is essential to initiate graft-vs-host disease (GVHD); however, critical APC subset remains to be elucidated. We compared the ability of dendritic cells (DCs) and B cells to initiate acute GVHD by an add-back study of MHC class II-expressing APCs (II(+/+)) into MHC class II-deficient (II(-/-)) mice that were resistant to CD4-dependent GVHD. Injection of host-derived, but not donor-derived, II(+/+) DCs or host-derived II(+/+) B cells, was sufficient to break GVHD resistance of II(-/-) mice and induced lethal acute GVHD. By contrast, host-derived II(+/+) B cells, both naive and LPS stimulated, failed to induce activation or tolerance of donor CD4(+) T cells. Similarly, in a model of CD8-dependent GVHD across MHC class I mismatch injection of allogeneic DCs, but not B cells, induced robust proliferation of donor CD8(+) T cells and broke GVHD resistance of chimeric recipients in which APCs were syngeneic to donors. These results demonstrate that host-derived DCs are critical in priming donor CD4(+) and CD8(+) T cells to cause GVHD, and selective targeting of host DCs may be a promising strategy to prevent GVHD.
Duffner
Ulrich A
UA
Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, MI 48109, USA.
Maeda
Yoshinobu
Y
Cooke
Kenneth R
KR
Reddy
Pavan
P
Ordemann
Rainer
R
Liu
Chen
C
Ferrara
James L M
JL
Teshima
Takanori
T
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II