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A Novel Mouse Model for Invariant NKT Cell Study¹

Hiroshi Wakao^2,*,, Hiroshi Kawamoto, Sakura Sakata, Kimiko Inoue^¶, Atsuo Ogura^¶, Rika Wakao, Atsushi Oda^* and Hiroyoshi Fujita^*

^* Environmental Biology, School of Medicine, Hokkaido University, Sapporo, Japan; Laboratory for Immune Regulation, Laboratory for Lymphocyte Development, and Developmental Genetics Group, RIKEN, Research Center for Allergy and Immunology, Yokohama-shi, Japan; and ^¶ Bioresource Engineering Division, RIKEN, Bioresource Center, Tsukuba, Japan

We have generated a novel mouse model harboring the in-frame rearranged TCRV specific for invariant NKT (iNKT) cells (V14-J18) on one allele by crossing the mouse cloned from NKT cells with wild-type mice. This genomic configuration would ensure further rearrangement and expression of TCRV14-J18 under the endogenous promoters and enhancers. Mice harboring such an in-frame rearranged TCRV (V14-J18 mouse) possessed an increase in iNKT cells in the thymus, liver, spleen, and bone marrow. Intriguingly, both Th1- and Th2-type cytokines were produced upon stimulation with Galactosylceramide, an agonist of iNKT cells, and the IgE level in the serum remained unaffected in the V14-J18 mouse. These features markedly distinguish the nature of iNKT cells present in the V14-J18 mouse from that of iNKT cells found in the V14-J18 transgenic mouse. Besides these, the expression of TCRV cells remained intact, and the use of the TCRV repertoire in iNKT cells was highly biased to TCRV8 in the V14-J18 mouse. Furthermore, Galactosylceramide-CD1d dimer-reactive immature iNKT cells expressed less Rag2 as compared with the conventional immature T cells at the positive selection stage. Cell cycle analysis on the thymocytes revealed that no particular subset proliferated more vigorously than the others. Crossing the V14-J18 mouse with the CD1d knockout mouse revealed a novel population of iNKT cells whose coreceptor expression profile was similar to that assigned to iNKT precursor cells. These mice will be useful for the study on the development of iNKT cells as well as on their functions in the immune system.

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 work was supported by RIKEN and in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A. Ogura).

² Address correspondence and reprint requests to Dr. Hiroshi Wakao, Environmental Biology, School of Medicine, Hokkaido University N15W7 Sapporo 060-8638 Japan. E-mail address: hwakao{at}med.hokudai.ac.jp

³ Abbreviations used in this paper: iNKT, invariant NKT; DP, double positive; GalCer, Galactosylceramide; Tg, transgenic; SP, single positive; DC, dendritic cell; HPRT, hypoxanthine phosphoribosyltransferase; DN, double negative; iIEL, intestinal intraepithelial lymphocyte.

This article has been cited by other articles:

				H. Wakao, R. Wakao, S. Sakata, K. Iwabuchi, A. Oda, and H. Fujita In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer FASEB J, July 1, 2008; 22(7): 2223 - 2231. [Abstract] [Full Text] [PDF]