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) 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.
Matsumoto
Goichi
G
Department of Oral and Maxillofacial Surgery, Kanagawa Dental College, Inaoka, Yokosuka, Japan. gmatsu@kdcdnet.ac.jp
Kubota
Eiro
E
Omi
Yasushi
Y
Lee
Ushaku
U
Penninger
Josef M
JM
D000818:Animals; D017951:Antigen Presentation; D002448:Cell Adhesion; D004268:DNA-Binding Proteins / Q000235:genetics; D050990:GATA3 Transcription Factor; D005699:Galactosylceramides / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D005699:Galactosylceramides; C494748:Gata3 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D015534:Trans-Activators; D015847:Interleukin-4; D007371:Interferon-gamma