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Clin Exp Immunol ; 185(1): 107-18, 2016 07.
Article in English | MEDLINE | ID: mdl-26990855

ABSTRACT

Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8(+) T cells were stimulated antigen-dependently with peptide-major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN)-γ and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8(+) CTLs, which was confirmed based on the reduced production of IFN-γ and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocyte-specific protein tyrosine kinase (Lck) and CD3ζ after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8(+) T cells and affects various elements of T cell activation.


Subject(s)
Antigen-Presenting Cells/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Lymphocyte Activation/drug effects , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Regulatory/drug effects , Antigen-Presenting Cells/cytology , Antigen-Presenting Cells/immunology , CD28 Antigens/genetics , CD28 Antigens/immunology , CD3 Complex/genetics , CD3 Complex/immunology , Cell Communication/drug effects , Cell Communication/immunology , Cell Line, Tumor , Coculture Techniques , Gene Expression Regulation , Granzymes/antagonists & inhibitors , Granzymes/genetics , Granzymes/immunology , Humans , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/genetics , Interferon-gamma/immunology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/immunology , MicroRNAs/genetics , MicroRNAs/immunology , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/immunology , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/immunology , Primary Cell Culture , RNA, Messenger/genetics , RNA, Messenger/immunology , Signal Transduction , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/immunology
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