Granulocyte colony‐stimulating factor impairs CD8 + T cell functionality by interfering with central activation elements

Summary 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.