TRAIL(+) NK cells control CD4(+) T cell responses during chronic viral infection to limit autoimmunity
- Schuster, IS; Wikstrom, ME; Brizard, G; Coudert, JD; Estcourt, MJ; Manzur, M; O'Reilly, LA; Smyth, MJ; Trapani, JA; Hill, GR; Andoniou, CE; Degli-Esposti, MA;
Publication Year 2014-10-16, Volume 41, Issue #4, Page 646-56
- Journal Title
- Publication Type
- Journal Article
- 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.
- Cell Press
- WEHI Research Division(s)
- Molecular Genetics Of Cancer
- Publisher's Version
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Creation Date: 2014-11-14 01:51:46Last Modified: 0001-01-01 12:00:00