Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell generation.
NKT cells from C57Bl/6 mice are known to be the initial cellular source of IL-4 that acts as a trigger for Th2 cell differentiation. CC-chemokine ligand 2 (CCL2) has been described as an initial stimulator of IL-4 production by these cells; however, IL-4 was not produced by NKT cells from BALB/c mice even when Th2 cell responses were established in these mice. In this study, we found a new pathway for CCL2-associated Th2 cell generation in BALB/c mice. Splenic T cells from BALB/c mice produced IL-4 in response to CCL2 stimulation. However, IL-4 production was not seen in cultures of splenic T cells from CD1-/- mice (BALB/c origin), whereas, in the presence of CCL2, splenic T cells from CD1-/- mice produced IL-4 when NKT cells from wild-type mice were added. CCL2 induced IL-4 in cultures of NKT cells cocultured with naive T cells, but IL-4 was not produced by these cells cultured separately with CCL2. Interestingly, IL-4 was produced by naive T cells cocultured with NKT cells that were previously treated with CCL2 (CCL2-NKT cells). In addition, IL-4 was produced by naive T cells supplemented with a culture supernatant of CCL2-NKT cells. These results indicate that, through the production of a soluble factor(s) other than IL-4, NKT cells play a role in the CCL2-associated generation of Th2 cells.
Fujita
Kazuhiko
K
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
Kobayashi
Makiko
M
Brutkiewicz
Randy R
RR
Hanafusa
Toshiaki
T
Herndon
David N
DN
Suzuki
Fujio
F
D000818:Animals; D018932:Chemokine CCL2 / Q000502:physiology*; D018920:Coculture Techniques; D015847:Interleukin-4 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015847:Interleukin-4