In previous studies, the authors showed that NKT cells derived from the liver can promote antitumour immune responses in two model systems: mice injected with the 3-methylcholanthrene-induced sarcoma cell line MCA-1, and mice injected with the melanoma cell line B16F10. Using these models, it was shown that mice that lack T-cell receptor (TCR) α-chains that contain Jα18 (denoted TCR Jα18), which are deficient in NKT cells, are more susceptible to tumour growth. In both tumour models, the ability of the NKT cells to promote antitumour responses was dependent on their production of interferon-γ.
Previous reports have shown that there are at least two phenotypically distinct subsets of NKT cells in mice and humans — CD4+ and CD4− NKT cells — and that these subsets show differential cytokine production in vitro. To test the idea that NKT-cell subsets are functionally distinct, as well as phenotypically distinct, the authors isolated NKT cells from the spleen, thymus and liver, then adoptively transferred these cells to TCR Jα18-deficient mice that had been injected with MCA-1. Only the liver-derived NKT cells could completely inhibit tumour growth, and this protection was found to be provided mainly by the CD4− population of NKT cells. The inability of thymus-derived NKT cells to confer protection was not a consequence of their impaired survival after transfer, because they were easily detectable in the liver and other organs for at least 1 week after transfer.
This is a preview of subscription content, access via your institution
