Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granul
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2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells 1†
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Yang Zhou , Leqing Cao , Huidong Guo , Yan Hong , Ming Wang , Ke Wang , 1,2* 1* Xiaojun Huang & Yingjun Chang 1
Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, 2
Beijing Key Laboratory of HSCT, Peking University, Beijing 100044, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100044, China Received March 3, 2020; accepted June 9, 2020; published online September 1, 2020
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 GCSF-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. granulocyte colony-stimulating factor, graft-versus-host disease, mouse model, Th2 polarization Citation:
Zhou, Y., Cao, L., Guo, H., Hong, Y., Wang, M., Wang, K., Huang, X., and Chang, Y. (2020). 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 63, https://doi.org/10.1007/s11427-020-1754-6
INTRODUCTION Acute graft-versus-host disease (aGVHD) is a fatal complication of allogeneic stem cell transplantation (allo-SCT) with severe morbidity and mortality (Liu et al., 2019; Yu et al., 2019; Zeiser and Blazar, 2017). It is a multiorgan inflammatory syndrome, mainly initialized by the influx of donor-derived alloreactive T cells into target organs. At an early stage, donor T cells are activated by the interaction †Contributed equally to this work *Corresponding authors (Xiaojun Huang, email: [email protected]; Yingjun Chang, email: [email protected])
between the T-cell receptor and the antigen-MHC complex, costimulatory molecules, and cytokines. A
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