title: Profound depletion of host conventional dendritic cells, plasmacytoid dendritic cells, and B cells does not prevent graft-versus-host disease induction.
abstract: The efficacy of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD). Host hematopoietic APCs are important initiators of GVHD, making them logical targets for GVHD prevention. Conventional dendritic cells (DCs) are key APCs for T cell responses in other models of T cell immunity, and they are sufficient for GVHD induction. However, we report in this article that in two polyclonal GVHD models in which host hematopoietic APCs are essential, GVHD was not decreased when recipient conventional DCs were inducibly or constitutively deleted. Additional profound depletion of plasmacytoid DCs and B cells, with or without partial depletion of CD11b(+) cells, also did not ameliorate GVHD. These data indicate that, in contrast with pathogen models, there is a surprising redundancy as to which host cells can initiate GVHD. Alternatively, very low numbers of targeted APCs were sufficient. We hypothesize the difference in APC requirements in pathogen and GVHD models relates to the availability of target Ags. In antipathogen responses, specialized APCs are uniquely equipped to acquire and present exogenous Ags, whereas in GVHD, all host cells directly present alloantigens. These studies make it unlikely that reagent-based host APC depletion will prevent GVHD in the clinic.
authors.affiliation: Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Jennifer
authors.initials: J
authors.lastname: McNiff
authors.forename: Catherine
authors.initials: C
authors.lastname: Matte-Martone
authors.forename: Hung Sheng
authors.initials: HS
authors.lastname: Tan
authors.forename: David M
authors.initials: DM
authors.lastname: Rothstein
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D039481:CD11b Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004167:Diphtheria Toxin; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D014184:Transplantation, Homologous
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D004167:Diphtheria Toxin; D007519:Isoantigens