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.
Original language | English (US) |
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Pages (from-to) | 107-118 |
Number of pages | 12 |
Journal | Clinical and Experimental Immunology |
Volume | 185 |
Issue number | 1 |
DOIs | |
State | Published - Jul 1 2016 |
Keywords
- antigen-specific T cells
- G-CSF
- immunotherapy
- mobilization
- T cell activation
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy