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Cutting Edge: Programmed Death-1/Programmed Death Ligand 1 Interaction Regulates the Induction and Maintenance of Invariant NKT Cell Anergy¹

Woo-Sung Chang^*, Ji-Yeon Kim^*, Yeon-Jeong Kim^*, Yun-Sun Kim^*, Jung-Mi Lee^*, Miyuki Azuma, Hideo Yagita and Chang-Yuil Kang^2,*

^* Laboratory of Immunology and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea; Department of Molecular Immunology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan

Invariant NKT (iNKT) cells are a distinct subset of T lymphocytes that recognize glycolipid Ags. Upon TCR stimulation, iNKT cells promptly secrete a wide range of cytokines and therefore have been investigated as a target for immunotherapy. However, after primary activation, iNKT cells become hyporesponsive toward their ligand (anergy). The further mechanism behind iNKT cell anergy is poorly understood. We found that a low level of programmed death-1 (PD-1) was constitutively expressed on iNKT cells and that PD-1 expression was increased after stimulation and lasted at least 2 mo. Moreover, not only did blocking of the PD-1/PD ligand 1 (PD-L1) pathway prevent the induction of anergy in iNKT cells, but anergic iNKT cells also recovered responsiveness and these "rescued" cells efficiently mediated antitumor immunity. Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by Korea Science and Engineering Foundation (KOSEF) National Research Laboratory Program Grant No. R0A-2008-000-20113-0 funded by the Korean government (Ministry of Education, Science, and Technology).

² Address correspondence and reprint requests to Dr. Chang-Yuil Kang, Laboratory of Immunology and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. E-mail address: cykang{at}snu.ac.kr

³ Abbreviations used in this paper: NKT, natural killer T; iNKT, invariant NKT; GC, -galactosylceramide; PD-1, programmed death-1; PD-L1, PD ligand 1; PD-L2, PD ligand 2.

⁴ The online version of this article contains supplemental material.

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