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

✍ Scribed by Gourapura J. Renukaradhya; Venkataraman Sriram; Wenjun Du; Jacquelyn Gervay-Hague; Luc Van Kaer; Randy R. Brutkiewicz

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 411 KB
• Volume: 118
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21764

✦ Synopsis

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. © 2006 Wiley‐Liss, Inc.