NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

• Published in: PLoS pathogens Vol. 15; no. 4; p. e1007725
• Main Authors: Pallmer, Katharina, Barnstorf, Isabel, Baumann, Nicolas S, Borsa, Mariana, Jonjic, Stipan, Oxenius, Annette
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2019; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Antigen presentation; Antiviral agents; B cells; Biology and Life Sciences; CD8 antigen; Chronic infection; Computer architecture; Crosstalk; Cytokines; Cytomegalovirus; Cytotoxicity; Dendritic cells; Disruption; Health aspects; Immune response; Infection; Infections; Killer cells; Ligands; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Metastasis; Mice; Natural killer cells; Novels; Proteins; Research and Analysis Methods; Spleen; T cells; Toxicity; Viral infections; Viruses; Weight loss; Switzerland
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007725

Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Using activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1gfp/gfp) mice, we found increased numbers of virus-specific CD8 T cells, leading to enhanced virus control during acute LCMV infection. Furthermore, virus-specific CD8 T cells were more activated in the absence of NCR1, resulting in exacerbated immunopathology, documented by weight loss, and superior virus control early during chronic LCMV infection. Transfer experiments of virus-specific CD8 T cells into NCR1 deficient hosts revealed a direct cross talk between NK and CD8 T cells. Studies on the splenic microarchitecture revealed pronounced disorganization of T cells in infected NCR1gfp/gfp mice, resulting in enhanced immunopathology and disruption of the T cell niche upon chronic LCMV infection. Our data show a novel pathway employed by NK cells to regulate antiviral CD8 T cell responses, namely direct recognition and elimination of activated CD8 T cells via NCR1 early during infection to protect the host from an overshooting T cell response.