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Cell Biology International (2007) 31, 257–262 (Printed in Great Britain)

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Proliferation of activated CD1d-restricted NKT cells is down-modulated by lymphocyte activation gene-3 signaling via cell cycle arrest in S phase

Hyun‑Jung Byun^ab1, Woon‑Won Jung^c1, Dong‑Sup Lee^d, Sanghee Kim^e, Sang Joon Kim^f, Chung‑Gyu Park^g, Hee Yong Chung^b and Taehoon Chun^a*

^aDivision of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Sung-Buk Ku, Anam-Dong, Seoul 136-701, South Korea
^bDepartment of Microbiology and Immunology, School of Medicine, Hanyang University, Seoul 133-791, South Korea
^cMyGene Bioscience Institute, Seoul 405-847, South Korea
^dLaboratory of Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea
^eNatural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-799, South Korea
^fDepartment of Surgery, Seoul National University College of Medicine, Seoul 110-799, South Korea
^gDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul 110-799, South Korea

Abstract

Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT cells may potentially prove to be useful therapeutic agents for the treatment of many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the regulating mechanisms of this unique T cell population remain to be defined. We found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen-specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells. Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell cycle arrest in the S phase. These results show that LAG-3 signaling on activated CD1d-restricted NKT cells may down-modulate NKT cell proliferation.

Key words: CD1d-restricted NKT cell, Cell cycle, Co-receptor, LAG-3.

¹These authors contributed equally to this study.

^*Corresponding author. Tel.: +82 2 3290 3069; fax: +82 2 3290 3507.

Received 18 July 2006/21 September 2006; accepted 5 November 2006