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

Gourapura J. Renukaradhya, Venkataraman Sriram, Wenjun Du, Jacquelyn Gervay-Hague, Luc Van Kaer, Randy R. Brutkiewicz

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41 Scopus citations


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 Jα18 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-γ 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.

Original languageEnglish
Pages (from-to)3045-3053
Number of pages9
JournalInternational Journal of Cancer
Issue number12
StatePublished - Jun 15 2006


  • CD1D molecules
  • Cytokines
  • Invariant NKT cells
  • RMA/S
  • T-cell lymphoma


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