TRAIL+ NK Cells Control CD4+ T Cell Responses during Chronic Viral Infection to Limit Autoimmunity

• Published in: Immunity (Cambridge, Mass.) Vol. 41; no. 4; pp. 646 - 656
• Main Authors: Schuster, Iona S., Wikstrom, Matthew E., Brizard, Geraldine, Coudert, Jerome D., Estcourt, Marie J., Manzur, Mitali, O’Reilly, Lorraine A., Smyth, Mark J., Trapani, Joseph A., Hill, Geoffrey R., Andoniou, Christopher E., Degli-Esposti, Mariapia A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.10.2014; Elsevier Limited
• Subjects: Adoptive Transfer; Animals; Antigens; Apoptosis - immunology; Autoimmunity - immunology; Breeding of animals; CD4-Positive T-Lymphocytes - immunology; Charitable foundations; Chronic Disease; Cytomegalovirus; Cytotoxicity, Immunologic - immunology; Data analysis; Design; Experiments; Herpesviridae Infections - immunology; Immune system; Infections; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Knockout; Murine cytomegalovirus; Muromegalovirus - immunology; NK Cell Lectin-Like Receptor Subfamily K - biosynthesis; Salivary Glands - immunology; Salivary Glands - pathology; Salivary Glands - virology; TNF-Related Apoptosis-Inducing Ligand - immunology; Viral infections
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2014.09.013

Natural killer (NK) cells have been reported to control adaptive immune responses that occur in lymphoid organs at the early stages of immune challenge. The physiological purpose of such regulatory activity remains unclear, because it generally does not confer a survival advantage. We found that NK cells specifically eliminated activated CD4+ T cells in the salivary gland during chronic murine cytomegalovirus (MCMV) infection. This was dependent on TNF-related apoptosis inducing ligand (TRAIL) expression by NK cells. Although NK cell-mediated deletion of CD4+ T cells prolonged the chronicity of infection, it also constrained viral-induced autoimmunity. In the absence of this activity, chronic infection was associated with a Sjogren’s-like syndrome characterized by focal lymphocytic infiltration into the glands, production of autoantibodies, and reduced saliva and tear secretion. Thus, NK cells are an important homeostatic control that balances the efficacy of adaptive immune responses with the risk of developing autoimmunity. [Display omitted] •A novel TRAIL+ NK cell subset regulates immune responses in chronic viral infection•TRAIL+ NK cells eliminate activated CD4+ T cells, but lack antiviral capacity•Development of autoimmune disease is constrained by TRAIL+ NK cells Natural killer (NK) cells can regulate adaptive immunity but the physiological purpose of this has been unclear. Degli-Esposti and colleagues demonstrate that NK cells utilize TRAIL to limit CD4+ T cell responses during chronic viral infection to constrain the development of autoimmunity.