G-CSF induces a potentially tolerant gene and immunophenotype profile in T cells in vivo

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-07, Vol.132 (1), p.83-92
• Main Authors: Toh, Han C, Sun, Li, Soe, Yatanar, Wu, Yonghui, Phoon, Yee P, Chia, Whay K, Wu, Jeanie, Wong, Kee Y, Tan, Patrick
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Biological and medical sciences; Blood Donors; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cluster Analysis; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; G-CSF; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Mobilization; Humans; Immune tolerance; Immunophenotyping; Interleukin-17 - metabolism; Nuclear Receptor Subfamily 1, Group F, Member 3; Receptors, Retinoic Acid - genetics; Receptors, Thyroid Hormone - genetics; Reverse Transcriptase Polymerase Chain Reaction; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th1 Cells - metabolism; Th17; Th2 Cells - metabolism; Treg
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.03.509

Abstract G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune tolerant profile with upregulation of genes related to Th2 and Treg cells, downregulation of genes associated with Th1 cells, cytotoxicity, antigen presentation and graft-versus-host disease (GVHD) and overexpression of negative regulators of Th17 differentiation. Immunophenotyping revealed that during G-CSF exposure donors had reduced levels of T cells with a Th17 phenotype (CD4+IL-17A+CCR6+IL-23R+), more than three times lower compared to normal controls. G-CSF also led to increased levels of CD4+CD25high CD45RO+ Treg cells. Furthermore, mRNA levels of RORγt , a Th17-specific transcription factor, decreased in T cells isolated from G-CSF-mobilized PBSC harvests. Th17 cells have been implicated in autoimmune diseases and GVHD pathophysiology. Our study is the first to report the effect of G-CSF on the Th17 subpopulation.