Effect of upregulated TLR2 expression from G-CSF-mobilized donor grafts on acute graft-versus-host disease

Int Immunopharmacol. 2015 Dec;29(2):488-493. doi: 10.1016/j.intimp.2015.10.007. Epub 2015 Oct 20.

Abstract

Our previous study demonstrated that G-CSF treatment increased the expression of TLR2 in donor grafts; this contributed to rapid engraftment after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. In the current study, we investigated the effects of upregulated TLR2 expression in G-CSF-mobilized donor grafts on acute graft-versus-host disease (GVHD). We found that TLR2 was highly expressed on myeloid cell populations but not T and B cells from the spleens of G-CSF-treated donor mice. After transplantation, the mortality and disease severity in recipients were not significantly different between G-CSF-treated TLR2-/- and wt donor grafts. Although endogenous TLR2 ligand was detected in the serum of both recipients, T cells from TLR2-/- and wt donors have the same ability regarding alloreactivity. Moreover, the blockade of TLR2 signaling in recipients by administering anti-TLR2 blocking antibody after BMT did not lead to a significant difference in acute GVHD compared with control IgG treatment. However, the hematopoietic ability of G-CSF-mobilized lin−c-kit+ HSCs from TLR2-/- donor grafts was lower than that from wt donor grafts. Our results demonstrate that upregulated TLR2 expression in G-CSF-mobilized donor grafts has no effect on acute GVHD, suggesting that TLR2 is a valuable target for increasing HSCT efficiency in order to enhance engraftment without exacerbating acute GVHD.

Keywords: GVHD; Peripheral blood stem cell transplantation; TLR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Graft vs Host Disease / immunology*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Transplantation / methods
  • Mice
  • Mice, Knockout
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • Stem Cell Transplantation
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 4 / biosynthesis*
  • Toll-Like Receptor 4 / genetics

Substances

  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Granulocyte Colony-Stimulating Factor