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 Brutkiewicz

Research output: Contribution to journalArticle

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Abstract

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
Volume118
Issue number12
DOIs
StatePublished - Jun 15 2006

Fingerprint

Natural Killer T-Cells
T-Cell Lymphoma
Immunity
Knockout Mice
Interleukin-13
Cytotoxic T-Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Innate Immunity
Cell Count
Cytokines
Antibodies
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibition of antitumor immunity by invariant natural killer T cells in a T-cell lymphoma model in vivo. / Renukaradhya, Gourapura J.; Sriram, Venkataraman; Du, Wenjun; Gervay-Hague, Jacquelyn; Van Kaer, Luc; Brutkiewicz, Randy.

In: International Journal of Cancer, Vol. 118, No. 12, 15.06.2006, p. 3045-3053.

Research output: Contribution to journalArticle

Renukaradhya, Gourapura J. ; Sriram, Venkataraman ; Du, Wenjun ; Gervay-Hague, Jacquelyn ; Van Kaer, Luc ; Brutkiewicz, Randy. / Inhibition of antitumor immunity by invariant natural killer T cells in a T-cell lymphoma model in vivo. In: International Journal of Cancer. 2006 ; Vol. 118, No. 12. pp. 3045-3053.
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