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

Research output: Contribution to journalArticle

214 Citations (Scopus)

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
Externally publishedYes

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Inbred NOD Mouse
Natural Killer Cells
NK Cell Lectin-Like Receptor Subfamily K
Ligands
1-Phosphatidylinositol 4-Kinase
Type 1 Diabetes Mellitus
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Ogasawara, K., Hamerman, J. A., Hsin, H., Chikuma, S., Bour-Jordan, H., Chen, T., ... 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

Impairment of NK cell function by NKG2D modulation in NOD mice. / Ogasawara, Kouetsu; Hamerman, Jessica A.; Hsin, Honor; Chikuma, Shunsuke; Bour-Jordan, Helene; Chen, Taian; Pertel, Thomas; Carnaud, Claude; Bluestone, Jeffrey A.; Lanier, Lewis L.

In: Immunity, Vol. 18, No. 1, 01.01.2003, p. 41-51.

Research output: Contribution to journalArticle

Ogasawara, K, Hamerman, JA, Hsin, H, Chikuma, S, Bour-Jordan, H, Chen, T, Pertel, T, Carnaud, C, Bluestone, JA & Lanier, LL 2003, 'Impairment of NK cell function by NKG2D modulation in NOD mice', Immunity, vol. 18, no. 1, pp. 41-51. https://doi.org/10.1016/S1074-7613(02)00505-8
Ogasawara K, Hamerman JA, Hsin H, Chikuma S, Bour-Jordan H, Chen T et al. Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity. 2003 Jan 1;18(1):41-51. https://doi.org/10.1016/S1074-7613(02)00505-8
Ogasawara, Kouetsu ; Hamerman, Jessica A. ; Hsin, Honor ; Chikuma, Shunsuke ; Bour-Jordan, Helene ; Chen, Taian ; Pertel, Thomas ; Carnaud, Claude ; Bluestone, Jeffrey A. ; Lanier, Lewis L. / Impairment of NK cell function by NKG2D modulation in NOD mice. In: Immunity. 2003 ; Vol. 18, No. 1. pp. 41-51.
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