Mouse Vα14i natural killer T cells are resistant to cytokine polarization in vivo

被引:203
作者
Matsuda, JL
Gapin, L
Baron, JL
Sidobre, S
Stetson, DB
Mohrs, M
Locksley, RM
Kronenberg, M
机构
[1] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
[2] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
[3] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Microbiol Immunol, San Francisco, CA 94143 USA
关键词
D O I
10.1073/pnas.1332805100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8395 / 8400
页数:6
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