title: Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell generation.
abstract: 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.
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fujita
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: 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*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015847:Interleukin-4