Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 14, Pages 8395-8400Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1332805100
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Funding
- NCI NIH HHS [R01 CA52511, R01 CA052511] Funding Source: Medline
- NIAID NIH HHS [AI30663, R01 AI030663] Funding Source: Medline
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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 Valpha14 rearrangement (Valpha14i 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 Valpha14i NKT cells contained IL-4 and IFN-gamma mRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by Valpha14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The Valpha14i 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 Valpha24i 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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