Impairment of NK cell function by NKG2D modulation in NOD mice

Kouetsu Ogasawara, Jessica A. Hamerman, Honor Hsin, Shunsuke Chikuma, Helene Bour-Jordan, Taian Chen, Thomas Pertel, Claude Carnaud, Jeffrey A. Bluestone, Lewis L. Lanier

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Abstract

Nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus, have a defect in natural killer (NK) cell-mediated functions. Here we show impairment in an activating receptor, NKG2D, in NOD NK cells. While resting NK cells from C57BL/6 and NOD mice expressed equivalent levels of NKG2D, upon activation NOD NK cells but not C57BL/6 NK cells expressed NKG2D ligands, which resulted in downmodulation of the receptor. NKG2D-dependent cytotoxicity and cytokine production were decreased because of receptor modulation, accounting for the dysfunction. Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2D-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands.

Original languageEnglish
Pages (from-to)41-51
Number of pages11
JournalImmunity
Volume18
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Ogasawara, K., Hamerman, J. A., Hsin, H., Chikuma, S., Bour-Jordan, H., Chen, T., Pertel, T., Carnaud, C., Bluestone, J. A., & Lanier, L. L. (2003). Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity, 18(1), 41-51. https://doi.org/10.1016/S1074-7613(02)00505-8