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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5637-5645.
Prepublished online as a Blood First Edition Paper on April 16, 2008; DOI 10.1182/blood-2007-05-092866.
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IMMUNOBIOLOGY
Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma
Gourapura J. Renukaradhya13,
Masood A. Khan13,
Marcus Vieira13,
Wenjun Du4,
Jacquelyn Gervay-Hague4, and
Randy R. Brutkiewicz13
1 Department of Microbiology and Immunology, Indiana University School of Medicine,
2 The Walther Oncology Center, and
3 The Walther Cancer Institute, Indianapolis, IN; and
4 Department of Chemistry, University of California, Davis
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)  chain rearrangement (V14J18 in mice; V24J18 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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