Functional Consequences of Altered Invariant Natural Killer T Cell Development and Effector Differentiation in the Vα14 Transgenic Mouse Model

Invariant Natural Killer T (iNKT) cells constitute a conserved population of unconventional T cells in mammals that regulate inflammation and immunity, through rapid and abundant production of cytokines and chemokines. iNKT cells differentiate into discrete functional subsets, iNKT1, iNKT2, and iNKT17, akin to conventional CD4 T helper cells. Mice that express a transgene for the canonical Vα14-Jα18 iNKT TCRα chain (Vα14 Tg) and harbour increased iNKT cell numbers have been widely used to study iNKT cells. In this thesis, our goal was to compare the development and functional response of iNKT cells in wild-type and Vα14 Tg mice. In Vα14 Tg mice, iNKT cells develop precociously and exhibit a strong bias towards the iNKT2 subset. Consequently, this bias impacts the ability of iNKT cells to prevent the growth of B16F10 melanoma tumours in Vα14 Tg mice. Therefore, past and future work involving these mice should be analyzed with caution.M.Sc