IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation
Protein & Cell
; (12): 863-871, 2013.
Article
em En
| WPRIM
| ID: wpr-757546
Biblioteca responsável:
WPRO
ABSTRACT
Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell transplantation. An animal model, xenogeneic GVHD (X-GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/c-Rag2⁻/⁻ IL-2RΓc⁻/⁻ (BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19⁺ B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19⁺ CD38(high) plasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the first to find in vivo expansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our findings show evidence of the involvement of B cells in X-GVHD and may have implications in the treatment of the disease.
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Índice:
WPRIM
Assunto principal:
Patologia
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Plasmídeos
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Sangue
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Imunoglobulina G
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Imunoglobulina M
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Linfócitos B
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Diferenciação Celular
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Interleucinas
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Proliferação de Células
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Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2013
Tipo de documento:
Article