Engagement of NK receptor NKG2D, but not 2B4, results in self-reactive CD8+T cells and autoimmune vitiligo

Andrew Zloza, Gretchen E. Lyons, Lukasz K. Chlewicki, Frederick J. Kohlhapp, Jeremy A. O'Sullivan, Andrew T. Lacek, Tamson V. Moore, Michael C. Jagoda, Vinay Kumar, José A. Guevara-Patio*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

In this study, we demonstrate that engagement of two different natural killer receptors (NKRs) can lead to contrasting effects in the development of self-reactive CD8+T cells and autoimmune vitiligo. Specifically, using a mouse model, we show that CD8+T-cell targeting of a melanocyte antigen, tyrosinase-related protein-1 (TRP-1) in combination with delivery of the NKG2D ligands (Rae-1ε or H60), results in strong CD8+T-cell responses against TRP-1 and in the development of autoimmune vitiligo. In contrast, targeting of TRP-1 in combination with delivery of CD48, the natural ligand for the NKR 2B4, leads to reduced formation of TRP-1-reactive CD8+T-cell responses and decreased development of vitiligo. These data indicate that autoimmune vitiligo is limited by insufficient signals, despite plentiful self-reactive T cells in the peripheral immune system. To our knowledge, this is the first experimental evidence supporting the role of NKRs in modulating CD8+T-cell autoimmune vitiligo. This study supports the utilization of NKR signaling as a therapeutic avenue toward prevention of vitiligo and other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalAutoimmunity
Volume44
Issue number8
DOIs
StatePublished - Dec 1 2011

Keywords

  • 2B4
  • Autoimmunity
  • NK receptor
  • NKG2D
  • Vitiligo

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zloza, A., Lyons, G. E., Chlewicki, L. K., Kohlhapp, F. J., O'Sullivan, J. A., Lacek, A. T., Moore, T. V., Jagoda, M. C., Kumar, V., & Guevara-Patio, J. A. (2011). Engagement of NK receptor NKG2D, but not 2B4, results in self-reactive CD8+T cells and autoimmune vitiligo. Autoimmunity, 44(8), 599-606. https://doi.org/10.3109/08916934.2011.593599