Essential role of LFA-1 in activating Th2-like responses by alpha-galactosylceramide-activated NKT cells

NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-gamma) and Th2 (IL-4) responses following stimulation of their invariant Valpha14 Ag receptor. The role of adhesion molecules in the activation of NKT cells by the Valpha14 ligand alpha-galactosylceramide (alpha-GalCer) r...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-10, Vol.173 (8), p.4976-4984
Main Authors: Matsumoto, Goichi, Kubota, Eiro, Omi, Yasushi, Lee, Ushaku, Penninger, Josef M
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Cell Adhesion
DNA-Binding Proteins - genetics
Galactosylceramides - pharmacology
GATA3 Transcription Factor
Gene Expression Regulation
Interferon-gamma - biosynthesis
Interleukin-4 - biosynthesis
Killer Cells, Natural - physiology
Lymphocyte Activation - drug effects
Lymphocyte Function-Associated Antigen-1 - physiology
Mice
Mice, Inbred C57BL
Th2 Cells - immunology
Trans-Activators - genetics
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Summary:NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-gamma) and Th2 (IL-4) responses following stimulation of their invariant Valpha14 Ag receptor. The role of adhesion molecules in the activation of NKT cells by the Valpha14 ligand alpha-galactosylceramide (alpha-GalCer) remains unclear. To address this issue, LFA-1-/- (CD11a-/-) mice were used to investigate IL-4 and IFN-gamma production by NKT cells following alpha-GalCer stimulation. Intriguingly, LFA-1-/- mice showed increased IL-4, IL-5, and IL-13 production and polarized Th2-type responses in response to alpha-GalCer in vitro and in vivo. Furthermore, the Th2-specific transcription factor GATA-3 was up-regulated in alpha-GalCer-activated NKT cells from LFA-1-/- mice. These results provide the first genetic evidence that the adhesion receptor LFA-1 has a crucial role in Th2-polarizing functions of NKT cells.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.8.4976