Acute graft-versus-host disease does not require alloantigen expression on host epithelium.
Alloantigen expression on host antigen-presenting cells (APCs) is essential to initiate graft-versus-host disease (GvHD); therefore, alloantigen expression on host target epithelium is also thought to be essential for tissue damage. We tested this hypothesis in mouse models of GvHD using bone-marrow chimeras in which either major histocompatibility complex class I or class II alloantigen was expressed only on APCs. We found that acute GvHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GvHD. These results pertain particularly to CD4-mediated GvHD but also apply, at least in part, to CD8-mediated GvHD. These results challenge current paradigms about the antigen specificity of GvHD effector mechanisms and confirm the central roles of both host APCs and inflammatory cytokines in acute GvHD.
Teshima
Takanori
T
Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, Michigan, USA.
Ordemann
Rainer
R
Reddy
Pavan
P
Gagin
Svetlana
S
Liu
Chen
C
Cooke
Kenneth R
KR
Ferrara
James L M
JL
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018183:Transplantation Chimera; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007519:Isoantigens; D014409:Tumor Necrosis Factor-alpha