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+CD25highCD45RO+ Treg cells. Furthermore, mRNA levels of RORgammat, 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blood Donors
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cluster Analysis
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Flow Cytometry
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Gene Expression Profiling / methods*
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Gene Expression Regulation / drug effects
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Granulocyte Colony-Stimulating Factor / pharmacology*
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Hematopoietic Stem Cell Mobilization*
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Humans
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Immunophenotyping
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Interleukin-17 / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid / genetics
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Receptors, Thyroid Hormone / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Th1 Cells / metabolism
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Th2 Cells / metabolism
Substances
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Interleukin-17
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Nuclear Receptor Subfamily 1, Group F, Member 3
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RORC protein, human
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Granulocyte Colony-Stimulating Factor