1. G-CSF induces a potentially tolerant gene and immunophenotype profile in T cells in vivo.
- Author
-
Toh HC, Sun L, Soe Y, Wu Y, Phoon YP, Chia WK, Wu J, Wong KY, and Tan P
- Subjects
- 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, Gene Expression Regulation drug effects, Humans, 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-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes, Helper-Inducer metabolism, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Th1 Cells metabolism, Th2 Cells metabolism, Gene Expression Profiling methods, Granulocyte Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cell Mobilization, T-Lymphocytes metabolism
- 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.
- Published
- 2009
- Full Text
- View/download PDF