Characterization of polyclonal type II NKT cells and their role in CpG oligodeoxynucleotides-mediated anti-tumor response (P2112)

Abstract CD1d-restricted NKT cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells which can be detected by α-GalCer (α-galactosylceramide) loaded CD1d tetramer and less-studied type II NKT cells which do not recognize α-GalCer. Here we characterized type II NKT cells on a polyclonal level by using an IL-4 reporter mouse model. We found type II NKT cells, like type I NKT cells, exhibit an activated phenotype and are dependent on the transcriptional regulator PLZF (promyelocytic leukemia zinc finger) and the adaptor molecule SAP (signaling lymphocyte activation molecule-associated protein) for their development. Compared to type I NKT cells, type II NKT cells produce lower levels of IFN-γ but comparable amounts of IL-13 in response to polyclonal TCR stimulation, suggesting they may play different roles in regulating immune responses. However, type II NKT cells can be activated by CpG oligodeoxynucletides to produce IFN-γ, but not IL-4 or IL-13. Importantly, CpG-activated type II NKT cells contribute to the anti-tumor effect of CpG in the B16 melanoma model. Taken together, our data reveal the characteristics of polyclonal type II NKT cells and their potential role in anti-tumor immunotherapy.