The influence of purified recombinant human TNF-α (rhuTNF-α) was assessed, alone and in combination with purified recombinant human IFN-γ (rhuIFN-γ), for its effects on enhancing release from human T lymphocytes of activities that stimulate colony formation by granulocyte-macrophage, erythroid, and multipotential progenitor cells. rhuTNF-α or rhuIFN-γ enhanced the release of CSF, whch were determined to be granulocyte-CSF and granulocyte-macrophage-CSF by human bone marrow colony assays, morphologic assessment of colony types, and neutralization studies with rabbit anti-human granulocyte-CSF and monoclonal mouse anti-human granulocyte-macrophage-CSF. The CSF were released only when PHA was used, whether or not rhuTNF-α and/or rhuIFN-γ were present while the lymphocytes conditioned the medium. T lymphocytes were sorted into subsets by using three-color immunofluorescence and a dye laser flow cytometry system with cells incubated with biotin anti-Leu-4 labeled with Texas Red, FITC-conjugated anti-Leu-3a, and phycoerythrin-conjugated anti-Leu-2a. Both the Leu-4+3a+2a- and the Leu-4+2a+3a- cells released CSF in response to PHA, but the release of CSF from PHA-stimulated lymphocytes was enhanced by rhuTNF-α and rhuIFN-γ only from the Leu-4+3a+2a- subset of cells. Use of the three-color cell sorting made it highly unlikely that NK cells were involved, because both sorted subsets were positive for Leu-4. rhuTNF-α and rhuIFN-γ synergized to enhance release of CSF such that low concentrations of each molecule, which were inactivae when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-α and IFN-γ in the release of CSF from subsets of T lymphocytes stimulated with PHA.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Immunology and Allergy