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

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.

• Authors: 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-Patiño
• Journal: Autoimmunity (Autoimmunity) Vol. 44 Issue 8 Pg. 599-606 (Dec 2011) ISSN: 1607-842X [Electronic] England
• PMID: 21913803 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• CD48 Antigen
• Cd244a protein, mouse
• Cd48 protein, mouse
• Ligands
• Mutant Proteins
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, Immunologic
• Signaling Lymphocytic Activation Molecule Family
• Oxidoreductases
• tyrosinase-related protein-1

Topics

• Animals
• Antigens, CD (genetics, metabolism)
• Autoimmune Diseases (immunology, metabolism)
• CD48 Antigen
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Ligands
• Lymphocyte Activation (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutant Proteins (genetics, metabolism)
• NK Cell Lectin-Like Receptor Subfamily K (metabolism)
• Oxidoreductases (genetics, metabolism)
• Receptors, Immunologic (metabolism)
• Signaling Lymphocytic Activation Molecule Family
• Vitiligo (immunology, metabolism)