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Impact of G-CSF on Donor TCR Clonal Diversity and T Cell Function During Donor HSC Mobilisation
Xinye Li1,2, Zhixi Chen1,2, Jie Chen2
1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Key Laboratory for Regenerative Medicine, Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
None:
Recombinant granulocyte colony-stimulating factor (G-CSF) is widely used to mobilise donor stem cells into peripheral blood for allogeneic haematopoietic stem cell transplantation (allo-HSCT). Studies have shown that G-CSF may reduce the incidence of acute graft-versus-host disease (aGVHD) following allo-HSCT by modulating T cell function. However, the patterns and mechanisms by which G-CSF regulates T cell function remain unclear. In this study, we used RNA sequencing combined with T cell receptor (TCR) immune repertoire sequencing to discover that G-CSF mobilisation leads to a reduction in donor TCR clonal diversity, downregulation of genes associated with TCR recombination, suppression of multiple antigen presentation processes, and varying degrees of downregulation in multiple T cell function-related signalling pathways. The results suggest that the pathway by which G-CSF mediates a low incidence of GVHD after allo-HSCT is by interfering with donor TCR recombination and antigen presentation processes, resulting in suppression of multiple T cell functions.
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