IL‐4‐producing NK T cells are biased towards IFN‐γ production by IL‐12. Influence of the microenvironment on the functional capacities of NK T cells

MC Leite‐De‐Moraes, G Moreau… - European journal of …, 1998 - Wiley Online Library
MC Leite‐De‐Moraes, G Moreau, A Arnould, F Machavoine, C Garcia, M Papiernik, M Dy
European journal of immunology, 1998Wiley Online Library
NK T cells are an unusual T lymphocyte subset capable of promptly producing several
cytokines after stimulation, in particular IL‐4, thus suggesting their influence in Th2 lineage
commitment. In this study we demonstrate that, according to the cytokines present in the
micro environment, NK T lymphocytes can preferentially produce either IL‐4 or IFN‐γ. In
agreement with our previous reports showing that their IL‐4‐producing capacity is strikingly
dependent on IL‐7, CD4− CD8− TCRα β+ NK T lymphocytes, obtained after expansion with …
Abstract
NK T cells are an unusual T lymphocyte subset capable of promptly producing several cytokines after stimulation, in particular IL‐4, thus suggesting their influence in Th2 lineage commitment. In this study we demonstrate that, according to the cytokines present in the micro environment, NK T lymphocytes can preferentially produce either IL‐4 or IFN‐γ. In agreement with our previous reports showing that their IL‐4‐producing capacity is strikingly dependent on IL‐7, CD4 CD8 TCRα β+ NK T lymphocytes, obtained after expansion with IL‐1 plus granulocyte‐macrophage colony‐stimulating factor, produced almost undetectable amounts of IL‐4 or IFN‐γ in response to TCR/CD3 cross‐linking. However, the capacity of these T cells to produce IFN‐γ is strikingly enhanced when IL‐12 is added either during their expansion or the anti‐CD3 stimulation, while IL‐4 secretion is always absent. A similar effect of IL‐12 on IFN‐γ production was observed when NK T lymphocytes were obtained after expansion with IL‐7. It is noteworthy that whatever cytokines are used for their expansion, IL‐12 stimulation, in the absence of TCR/CD3 cross‐linking, promotes consistent IFN‐γ secretion by NK T cells without detectable IL‐4 production. Experiments in vivo demonstrated a significant up‐regulation of the capacity of NK T cells to produce IFN‐γ after anti‐CD3 mAb injection when mice were previously treated with IL‐12. In conclusion, we provide evidence that the functional capacities of NK T cells, which ultimately will determine their physiological roles, are strikingly dependent on the cytokines present in their microenvironment.
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