title: Donor and host B cell-derived IL-10 contributes to suppression of graft-versus-host disease.
abstract: Graft-versus-host disease (GvHD) is a frequent life-threatening complication following allogeneic HSC transplantation (HSCT). IL-10 is a regulatory cytokine with important roles during GvHD, yet its relevant sources, and mode of action, remain incompletely defined in this disease. Using IL-10-deficient donor or host mice (BALB/c or C57BL/6, respectively) in a MHC-mismatched model for acute GvHD, we found a strongly aggravated course of the disease with increased mortality when either donor or host cells could not produce this cytokine. A lack of IL-10 resulted in increased allogeneic T-cell responses and enhanced activation of host DCs in spleen and MLNs. Remarkably, IL-10 was prominently produced by host- and donor-derived CD5(int) CD1d(int) TIM-1(int) B cells in this disease, and consistent with this, allogeneic HSCT resulted in exacerbated GvHD when mice lacking IL-10 expression in B cells were used as donor or host, compared with controls. Taken together, this study demonstrates that host and donor B cell-derived IL-10 provides a unique mechanism of suppression of acute GvHD, and suggests that DCs are the targets of this B cell-mediated suppressive effect. These findings open novel therapeutic possibilities based on the use of B cells to increase the feasibility of allogeneic HSCT.
authors.affiliation: Institute of Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.forename: Steve
authors.initials: S
authors.lastname: Prüfer
authors.forename: Berenice
authors.initials: B
authors.lastname: Rudolph
authors.forename: Andreas
authors.initials: A
authors.lastname: Kreft
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
mesh_terms: D064591:Allografts; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: B cells; Graft-versus-host disease; IL-10