Mouse V alpha 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 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.
Matsuda
Jennifer L
JL
La Jolla Institute for Allergy and Immunology, and Division of Biological Sciences, University of California, San Diego, CA, USA.
Gapin
Laurent
L
Baron
Jody L
JL
Sidobre
Stéphane
S
Stetson
Daniel B
DB
Mohrs
Markus
M
Locksley
Richard M
RM
Kronenberg
Mitchell
M
D000483:Alleles; D000818:Animals; D019013:CD40 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D003433:Crosses, Genetic; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*
D019013:CD40 Antigens; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma