Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro

• Published in: Cellular immunology 2018-03, Vol.325, p.23-32
• Main Authors: Malashchenko, Vladimir Vladimirovich, Meniailo, Maxsim Evgenievich, Shmarov, Viacheslav Anatolievich, Gazatova, Natalia Dinislamovna, Melashchenko, Olga Borisovna, Goncharov, Andrei Gennadievich, Seledtsova, Galina Victorovna, Seledtsov, Victor Ivanovich
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adult; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; CD25; CD28 Antigens - immunology; CD38; CD4-Positive T-Lymphocytes - immunology; Cytokines - biosynthesis; Female; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte Colony-Stimulating Factor - pharmacology; Healthy Volunteers; Humans; Immunologic Memory - drug effects; Interferon; Interferon-gamma - immunology; Interleukin; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Lymphocyte Activation - drug effects; Macrophage Activation - drug effects; Male; T-cell subset; T-Lymphocyte Subsets - immunology; T-Lymphocytes - drug effects
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2018.01.007

•T-cell activation stimulates the G-CSFR (CD114) expression on T-cells.•Upon T-cell activation, G-CSF enhances the proportion of CD38+ T cells.•G-CSF down-regulates INF-γ production and of up-regulates IL-4 production.•G-CSF is able to constrain T-cell-driven, pro-inflammatory responses. We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3+ T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA+/CD197+ naive T cells, CD45RA−/CD197+ central memory T cells, CD45RA−/CD197− effector memory T cells and CD45RA+/CD197− terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114+ T cells in central memory CD4+ T cell compartment. A dilution series of G-CSF (range, 0.1–10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38+ T cells in CD4+ naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4− central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells.