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Production of IL-10 by human natural killer cells stimulated with IL-2 and/or IL-12.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1998 Mar 15; Vol. 160 (6), pp. 2637-44. - Publication Year :
- 1998
-
Abstract
- Human NK cell activity can be augmented in vitro by stimulation with IL-2 or IL-12, both of which also induce the production of IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF by NK cells. For the first time, we demonstrate that freshly purified NK cells stimulated with IL-2 proliferated and produced IL-10 in a dose-dependent manner. IL-10 mRNA expression, as detected by semiquantitative reverse transcription-PCR, reached peak levels at 24 h. IL-10 protein was detectable on day 2 and further increased on days 3 and 6 as measured by ELISA. However, IL-12 alone induced neither substantial proliferation nor detectable IL-10 production by fresh NK cells, but it synergized with IL-2 in inducing IL-10 mRNA expression and protein synthesis. IL-10 production by activated NK cells was confirmed by intracytoplasmic cytokine staining by three-color immunofluorescence of CD16+ and/or CD56+ NK cells with anti-IL-10 antibody. IL-10 production by NK cells was further confirmed in the NK-like cell line, YT, which constitutively expressed IL-10 mRNA and protein. IL-12 alone did not induce NK proliferation, but it inhibited IL-2-induced proliferation. Neutralization of endogenously produced IL-10 with anti-IL-10 antibodies did not overcome the inhibition of IL-2-induced proliferation by IL-12. Together, these results demonstrate that IL-2 and IL-12 synergize to induce IL-10 production by human NK cells and that IL-12 inhibits IL-2 induced NK cell proliferation by an IL-10-independent mechanism.
- Subjects :
- Cells, Cultured
Flow Cytometry
Humans
Interleukin-10 genetics
Killer Cells, Natural metabolism
Lymphocyte Activation drug effects
Polymerase Chain Reaction
RNA, Messenger analysis
Interleukin-10 biosynthesis
Interleukin-12 pharmacology
Interleukin-2 pharmacology
Killer Cells, Natural drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 160
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 9510161