Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Sci China Life Sci. 2021 Jul;64(7):1087-1096. doi: 10.1007/s11427-020-1754-6. Epub 2020 Sep 1.

Abstract

Acute graft-versus-host disease (aGVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor (G-CSF) has been demonstrated to relieve the aGVHD reaction. However, the role of G-CSF-primed donor T cells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model (C57BL/6 into BALB/c) and found that recipient mice transplanted with G-CSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this aGVHD mouse model, especially in the lung and gut. Moreover, we found that T cells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator (ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated aGVHD, especially for its precise regulation in GVHD target organs.

Keywords: Th2 polarization; graft-versus-host disease; granulocyte colony-stimulating factor; mouse model.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / prevention & control*
  • Granulocyte Colony-Stimulating Factor / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology*
  • Transplantation, Homologous

Substances

  • Granulocyte Colony-Stimulating Factor