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Essential Role of LFA-1 in Activating Th2-Like Responses by -Galactosylceramide-Activated NKT Cells¹

Goichi Matsumoto^2,*, Eiro Kubota^*, Yasushi Omi^*, Ushaku Lee^* and Josef M. Penninger

^* Department of Oral and Maxillofacial Surgery, Kanagawa Dental College, Kanagawa, Japan; and Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria

NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-) and Th2 (IL-4) responses following stimulation of their invariant V14 Ag receptor. The role of adhesion molecules in the activation of NKT cells by the V14 ligand -galactosylceramide (-GalCer) remains unclear. To address this issue, LFA-1^–/– (CD11a^–/–) mice were used to investigate IL-4 and IFN- production by NKT cells following -GalCer stimulation. Intriguingly, LFA-1^–/– mice showed increased IL-4, IL-5, and IL-13 production and polarized Th2-type responses in response to -GalCer in vitro and in vivo. Furthermore, the Th2-specific transcription factor GATA-3 was up-regulated in -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.

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