Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma

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Graduate School of Biomedical Sciences; Department of Pathology

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Life Sciences | Medicine and Health Sciences


Natural killer T (NKT) cells are a T-cell subpopulation known to possess immunoregulatory functions and recognize CD1d molecules. The majority of NKT cells express an invariant T-cell receptor (TCR) alpha chain rearrangement (Valpha14 Jalpha18 in mice; Valpha24 Jalpha18 in humans) and are called type I NKT cells; all other NKT cells are type II. In the current study, we have analyzed the roles for these NKT-cell subsets in the host's innate antitumor response against a murine B-cell lymphoma model in vivo. In tumor-bearing mice, we found that type I NKT cells conferred protection in a CD1d-dependent manner, whereas type II NKT cells exhibited inhibitory activity. Pro- and anti-inflammatory cytokines secreted by splenocytes from tumor-bearing mice correlated with tumor progression. Myeloid cells (CD11b(+)Gr1(+)) were present in large numbers at the tumor site and in the spleen of tumor-bearing type I NKT-deficient mice, suggesting that antitumor immunosurveillance was inhibited by CD11b(+)Gr1(+) cells. Overall, these data suggest that there are distinct roles for NKT-cell subsets in response to a B-cell lymphoma in vivo, pointing to potential novel targets to be exploited in immunotherapeutic approaches against blood cancers.

DOI of Published Version



Blood. 2008 Jun 15;111(12):5637-45. Epub 2008 Apr 16. Link to article on publisher's site

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