Expression of Granulysin in Humanized Mouse Model System of Xenogeneic Graft-versus-Host-Disease
Date Issued
2011
Date
2011
Author(s)
Lan, Yu-Ling
Abstract
Although the involvement of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells) in the pathogenesis of graft-versus-host-disease (GVHD) have been well established, the cytotoxic proteins that are responsible for the skin and organ toxicity remains to be clarified. Recently a mechanism involving a cytotoxic protein, granulysin, was proposed. However, study on the functional role of granulysin in GVHD has been hampered by lack of appropriate mouse GVHD model due to the absence of granulysin gene in the mouse genome. Here, we developed a humanized immune system (HIS) mouse model with xenogenic-GVHD based on the intravenous injection of human umbilical cord blood mononuclear cells (UCBMCs) into sublethally irradiated NOD/Lt-scid IL2rγ null (NSG) mice. The HIS-X-GVHD mouse model exhibited human cells engraftment and human cytokine production with lymphocytic infiltration in the liver, spleen, lung, kidney and skin. Futhermore, immunohistochemistry demonstrated that the infiltrative lymphocytes in various organs were predominantly human CD45+ and CD8+ cells. Importantly, we found that granulysin was highly expressed in the liver, spleen, lung, kidney and skin. Besides, Serum granulysin levels were positively correlated with severity of GVHD. The HIS mouse model with X-GVHD provides the opportunity to investigate in vivo mechanisms of the regulation of granulysin, as well as to test the novel therapeutics for treatment of GVHD.
Subjects
graft-versus-host-disease
cytotoxic T lymphocytes
NK cells
granulysin
humanized immune system mouse model
umbilical cord blood mononuclear cells.
SDGs
Type
thesis
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