Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 185, Issue 1, Pages 107-118Publisher
WILEY
DOI: 10.1111/cei.12794
Keywords
antigen-specific T cells; G-CSF; immunotherapy; mobilization; T cell activation
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Funding
- Braukmann-Wittenberg-Herz-Stiftung
- Deutsche Forschungsgemeinschaft
- Integrated Research and Treatment Center Transplantation (IFB-Tx)
- German Federal Ministry of Education and Research [01EO0802]
- Hannover Biomedical Research School (HBRS)
- PhD programme 'Molecular Medicine'
- Deutsche Jose Carreras Leukamie-Stiftung [DJCLS F14/04]
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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)- 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- 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 CD3 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.
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