Inhibition of antitumor immunity by invariant natural killer T cells in a T-cell lymphoma model in vivo.

Renukaradhya GJ, Sriram V, Du W, Gervay-Hague J, Van Kaer L, Brutkiewicz RR
Int J Cancer. 2006 118 (12): 3045-53

PMID: 16395717 · DOI:10.1002/ijc.21764

We have investigated the role of the host's CD1d-dependent innate antitumor immune response in a murine T-cell lymphoma model in vivo. We found that C57BL/6 wildtype (WT) mice inoculated with RMA/S cells transfected with murine CD1d1 died at the same rate as mice inoculated with vector-transfected cells. In contrast, natural killer T (NKT) cell-deficient CD1d or Jalpha18 knockout mice inoculated with CD1d-transfected RMA/S cells survived significantly longer than mice inoculated with vector-transfected RMA/S cells, implicating the involvement of invariant NKT (iNKT) cells in inhibiting antitumor activity in vivo. In contrast to the mutant mice, which produced more of the proinflammatory cytokines IFN-gamma and GM-CSF, WT mice produced significantly elevated amounts of IL-13. Antitumor activity in the knockout mice was not due to the development of CD1d-specific cytotoxic T lymphocytes or circulating antibodies. However, iNKT cell numbers were elevated in tumor-bearing mice. Thus, iNKT cells may be playing a negative role in the host's antitumor immune response against T-cell lymphomas in a CD1d-dependent manner.

Copyright 2006 Wiley-Liss, Inc.

MeSH Terms (19)

Animals Antigens, CD1 Antigens, CD1d Cell Line, Tumor Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor Interferon-gamma Interleukin-13 Killer Cells, Natural Lymphocyte Activation Lymphoma, T-Cell Male Mice Mice, Inbred C57BL Mice, Knockout Time Factors

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