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Eur J Immunol. 2014 Jun;44(6):1857-65. doi: 10.1002/eji.201344081. Epub 2014 Mar 25.

Donor and host B cell-derived IL-10 contributes to suppression of graft-versus-host disease.

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1
Institute of Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.

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.

KEYWORDS:

B cells; Graft-versus-host disease; IL-10

PMID:
24643745
DOI:
10.1002/eji.201344081
[Indexed for MEDLINE]
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