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

• DOI: 10.1111/cei.12794
• Publication Date: 2016-03-19T02:09:28Z
• Authors: C E Bunse; S Tischer; J Lahrberg; M Oelke; C Figueiredo; R Blasczyk; B Eiz-Vesper
• Keywords: Mitogen-Activated Protein Kinase 1; 0301 basic medicine; Mitogen-Activated Protein Kinase 3; CD3 Complex; Primary Cell Culture; Antigen-Presenting Cells; Cell Communication; Lymphocyte Activation; Coculture Techniques; Granzymes; Interferon-gamma; MicroRNAs; 03 medical and health sciences; CD28 Antigens; Gene Expression Regulation; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Cell Line, Tumor; Granulocyte Colony-Stimulating Factor; Humans; RNA, Messenger; Signal Transduction; T-Lymphocytes, Cytotoxic

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