A novel mouse model for invariant NKT cell study
Wakao, H.; Kawamoto, H.; Sakata, S.; Inoue, K.; Ogura, A.; Wakao, R.; Oda, A.; Fujita, H.
Journal of Immunology 179(6): 3888-3895
2007
ISSN/ISBN: 0022-1767 PMID: 17785826 Document Number: 608269
We have generated a novel mouse model harboring the in-frame rearranged TCRV alpha specific for invariant NKT (iNKT) cells (V alpha 14-J alpha 18) 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 TCRV alpha 14-J alpha 18 under the endogenous promoters and enhancers. Mice harboring such an in-frame rearranged TCRVa (V alpha 14-J alpha 18 mouse) possessed an increase in iNKT cells in the thymus, liver, spleen, and bone marrow. Intriguingly, both Thl- and Th2-type cytokines were produced upon stimulation with aGalactosylceramide, an agonist of iNKT cells, and the IgE level in the serum remained unaffected- in the Va14-Ja18 mouse. These features markedly distinguish the nature of iNKT cells present in the V alpha 14-J alpha 18 mouse from that of iNKT cells found in the V alpha 14-J alpha 18 transgenic mouse. Besides these, the expression of TCRV gamma delta cells remained intact, and the use of the TCRV beta repertoire in iNKT cells was highly biased to TCRV beta 8 in the Va14-Ja18 mouse. Furthermore, alpha 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 V alpha 14-Ja alpha 18 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.