Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses

Silke Paust, et al. 2010. Nature Immunology 11, 1127-1136

Speaker: Shih-Ying Wu (吳思瑩)                                 Time: 14:00~15:00, May 11, 2011

Commentator: Dr. Chi-Chang Shieh (謝奇璋醫師)     Place: Room 601

Abstract

Natural killer (NK) cells are considered as a member of the innate immunity. However, some studies suggested that NK cells can mediate adaptive immunity without T cells and B cells. Similar to NKT cells, hapten-specific memory NK cells reside preferentially in the liver. The intrahepaticsurvival and homeostasis of NKT cells require surface expression of CXCR6 (CD186). However, the function of the CXCR6⁺ NK cells has not been investigated. To address this question, the authors transferred the hapten-sensitized hepatic or splenic NK cells to naïve Rag2^-/-/Il2rg^-/- mice and challenged the recipient mice 24 hr and 4 months later. They found that only hapten-sensitized hepatic NK cells could accumulate at the effector sites and develop specific immune response toward the different antigens. To assess more broadly whether NK cells could develop antiviral memory, they immunized the mice with noninfectious virus-like particles (VLPs) or UV-inactivated viruses from influenza, vascular stomatitis virus (VSV) or human immunodeficiency virus type 1 (HIV-1). They transferred the virus-sensitized hepatic NK cells into naïve Rag1^-/- or Rag2^-/-/Il2rg^-/-mice, and challenged the recipient mice with these viruses. They found that the sensitized hepatic NK cells had memory toward the viruses and could induce immune response to protect the host against lethal viral infection. Notably, CXCR6 played an important role in the NK cell memory. The authors used three complementary approaches to prove that CXCR6 is required for NK cell-mediated adaptive immunity to the haptens and viruses. CXCR6 could regulate the development and/or survival of hepatic CXCR6⁺ NK cells, but not recognize the antigens. Furthermore, when blocking the CXCR6-CXCL16 pathway in vitro, the cytotoxicity of sensitized hepatic NK cells would be enhanced. In summary, CXCR6 plays an important role in development of antigen-specific adaptive immunity of hepatic NK cells.

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