A Novel Mouse Model for Invariant NKT Cell Study

Abstract

We have generated a novel mouse model harboring the in-frame rearranged TCRVα specific for invariant NKT (iNKT) cells (Vα14-Jα18) 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 TCRVα14-Jα18 under the endogenous promoters and enhancers. Mice harboring such an in-frame rearranged TCRVα (Vα14-Jα18 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 αGalactosylceramide, an agonist of iNKT cells, and the IgE level in the serum remained unaffected in the Vα14-Jα18 mouse. These features markedly distinguish the nature of iNKT cells present in the Vα14-Jα18 mouse from that of iNKT cells found in the Vα14-Jα18 transgenic mouse. Besides these, the expression of TCRVγδ cells remained intact, and the use of the TCRVβ repertoire in iNKT cells was highly biased to TCRVβ8 in the Vα14-Jα18 mouse. Furthermore, αGalactosylceramide-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 Vα14-Jα18 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.