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

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 14 rearrangement (V 14i NKT cells) rapidly produce both IL-4 and IFN, 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 14i NKT cells contained IL-4 and IFNmRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by V 14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The V 14i NKT cells from primed mice retain the ability to produce IL-4 and IFN, but they are less effective at activating NK cells to produce IFN. Our data therefore indicate that V 14i NKT cells have a relatively inflexible immediate cytokine response, but that changes in their ability to induce IFNsecretion by NK cells may determine the extent to which they promote Th1 responses.