Inhibition of human granulocyte-macrophage colony formation by interleukin 2-treated lymphocytes is mediated by interferon gamma and tumor necrosis factor alpha.
We previously demonstrated that human granulocyte-macrophage colony (granulocyte-macrophage colony-forming units, CFU-GM) formation was inhibited by interleukin 2 (IL-2)-treated lymphocytes and their conditioned medium (CM). In the present study, the mechanism of this suppression was investigated. When anti-interferon (IFN)-gamma antibody or anti-tumor necrosis factor (TNF)-alpha antibody was added to CFU-GM agar culture with IL-2-treated lymphocytes or their CM, the inhibition of CFU-GM colony formation was partially abrogated, whereas anti-TNF-beta antibody did not abolish the inhibitory effects. When anti-IFN-gamma and anti-TNF-alpha antibodies were added simultaneously, full recovery of colony formation was observed. In the CM of IL-2-treated lymphocytes, detectable levels of IFN-gamma (81 +/- 15 U/ml) and TNF (3.1 +/- 1.1 U/ml) were found. Addition of IFN-gamma and TNF-alpha at these concentrations to the agar culture inhibited CFU-GM colony formation. Taken together, these results indicate that inhibition of human CFU-GM colony formation by IL-2-treated lymphocytes and their CM is mediated by IFN-gamma and TNF-alpha generated from IL-2-treated lymphocytes.
Takahashi
M
M
Department of Medicine, Tokyo Women's Medical College, Japan.
Oshimi
K
K
Mizoguchi
H
H
D000906:Antibodies / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008214:Lymphocytes / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma