A validation of the requirement for Vα14 NKT cells for tumor rejection using newly generated Traj18-deficient mice with undisturbed T cell receptor repertoire (#49)
Invariant natural killer T (NKT) cells are a unique lymphocyte subset characterized by the expression of a single invariant T cell receptor (TCR) α chain encoded by rearranged Trav11-Traj18 gene segments in mice, and TRAV10-TRAJ18 in humans. It is well established that NKT cells mediate adjuvant effects to activate various effector cell types in both innate and adaptive immune systems that facilitates the potent antitumor effects against MHC-negative and MHC-positive tumors, respectively.
It has, however, been reported that the “Jα18-deficient mice”, described in 1997 by our group, harbors perturbed repertoire of TCR α chain joining region that has raised concerns regarding the validity of experimental conclusions that were made by using this mouse line. Thus, to resolve this concern, we generated a novel Traj18-deficient mouse line by specifically targeting the Traj18 gene segment using Cre-Lox site-specific recombinase approach. The resultant mouse line, termed as Traj18-/-, was totally devoid of NKT cells in the thymus as well as in peripheral immune organs. Importantly, we confirmed the protective role of NKT cells against tumors by using the newly generated Traj18-/- mice lacking NKT cells but with intact development of T cell lineages that is evidenced by an undisturbed TCR α chain repertoire assessed by using the next generation sequencing.