Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma
Graduate School of Biomedical Sciences; Department of Pathology
Medical Subject Headings
Adoptive Transfer; Animals; Ascites; Cell Line, Tumor; Cytokines; Female; *Immunotherapy; Killer Cells, Natural; Lymphoma, B-Cell; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Myeloid Cells; Receptors, Antigen, T-Cell, alpha-beta; Spleen; Survival Rate; T-Lymphocyte Subsets
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.
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Citation: Blood. 2008 Jun 15;111(12):5637-45. Epub 2008 Apr 16. Link to article on publisher's site
Renukaradhya, Gourapura J.; Khan, Masood A.; Vieira, Marcus A. L.; Du, Wenjun; Gervay-Hague, Jacquelyn; and Brutkiewicz, Randy R., "Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma" (2008). GSBS Student Publications. 1482.