![]() Compared to T and B cells, NK cells stochastically express various germ-line encoded activating and inhibitory receptors. Natural killer (NK) cells play an essential role in eliminating cancerous and virus infected cells, they co-express Eomesodermin (EOMES) and Tbx21 T-box expressed in T cells (T-bet) and are able to produce cytotoxic mediators such as perforin/ granzyme B and Interferon (IFN)γ. 310030_166078 to AO).Ĭompeting interests: The authors have declared that no competing interests exist. This work was supported by ETH Zurich, the Swiss National Science Foundation (grant no. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Received: AugAccepted: MaPublished: April 17, 2019Ĭopyright: © 2019 Pallmer et al. PLoS Pathog 15(4):Įditor: Liisa Selin, University of Massachusetts Medical School, UNITED STATES Hence, NK cells curtail CD8 T cell responses to protect the host from immunopathological damage in an NCR1 dependent manner.Ĭitation: Pallmer K, Barnstorf I, Baumann NS, Borsa M, Jonjic S, Oxenius A (2019) NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection. However, the increased CD8 T cell responses led to severe immunopathology in the setting of chronic infection. The absence of NCR1 led to a more robust CD4 and CD8 T cell response and to superior viral control in acute and chronic LCMV infections. Here, we identified the activating NK cell receptor NCR1 to be involved in the regulation of CD8 T cell responses during acute and chronic LCMV infection. However, the detailed mechanisms of how NK cells control antiviral T cell responses is still poorly defined. The absence of NK cells leads to increased T cell immunity and thereby, to faster eradication of the virus. While NK cells are dispensable for control of LCMV, NK cells have the potential to shape adaptive immunity by regulating T cell responses. NK cells belong to the first line defense, being activated early following infection or exposure to malignant cells, and mediate their antiviral or anti-tumoral effect by direct cytotoxicity and inflammatory cytokine secretion. LCMV, which is part of the Arenaviridae family, is a well-established mouse model for acute and chronic virus infections, and it has allowed the identification of many immunological principles that were subsequently confirmed in human infections, such as CTL escape or CD8 T cell exhaustion. 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. Studies on the splenic microarchitecture revealed pronounced disorganization of T cells in infected NCR1 gfp/gfp mice, resulting in enhanced immunopathology and disruption of the T cell niche upon 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. 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. Using activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1 gfp/gfp) mice, we found increased numbers of virus-specific CD8 T cells, leading to enhanced virus control during acute LCMV infection. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. ![]()
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