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Expression of IFN-gamma upon triggering of activating Ly49D NK receptors in vitro and in vivo: Costimulation with IL-12 or IL- 18 overrides inhibitory receptors

  1. Author:
    Ortaldo, J. R.
    Young, H. A.

  2. Author Address

    Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, B-560,Rm 31-93, Ft Detrick, MD 21702 USA Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA Ortaldo JR Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, B-560,Rm 31-93, Ft Detrick, MD 21702 USA
    1. Year: 2003
  2. Journal: Journal of Immunology
    1. 170
    2. 4
    3. Pages: 1763-1769
  4. Type of Article: Article
  1. Abstract:

    NK cells can express both activating and inhibitory Ly49 receptors on their cell surface. When cells expressing both receptors are presented with a ligand, inhibition dominates the functional outcome. In this report we demonstrate that costimulation of the activating Ly49D murine NK cell receptor with IL-12 or IL-18 is capable of over-riding the inhibitory Ly49G2 receptor blockade for cytokine production both in vitro and in vivo. This synergy is mediated by and dependent upon Ly49D-expressing NK cells and results in significant systemic expression of IFN-gamma. This would place NK cells and their activating Ly-49 receptors as important initiators of microbial, antiviral, and antitumor immunity and provide a mechanism for the release of activating Ly49 receptors from inhibitory receptor blockade. The Journal of Immunology, 2003.

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