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Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8395-400. Epub 2003 Jun 26.

Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo.

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  • 1La Jolla Institute for Allergy and Immunology, and Division of Biological Sciences, University of California, San Diego, CA, USA.


Under different circumstances, natural killer T (NKT) cells can cause a T helper (Th) 1 or a Th2 polarization of immune responses. We show here, however, that mouse NKT cells with an invariant V alpha 14 rearrangement (V alpha 14i NKT cells) rapidly produce both IL-4 and IFN-gamma, and this pattern could not be altered by methods that polarize naive CD4+ T cells. Surprisingly, although cytokine protein was detected only after activation, resting V alpha 14i NKT cells contained IL-4 and IFN-gamma mRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by V alpha 14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The V alpha 14i NKT cells from primed mice retain the ability to produce IL-4 and IFN-gamma, but they are less effective at activating NK cells to produce IFN-gamma. Our data therefore indicate that V alpha 14i NKT cells have a relatively inflexible immediate cytokine response, but that changes in their ability to induce IFN-gamma secretion by NK cells may determine the extent to which they promote Th1 responses.

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