Frontiers in Cellular and Infection Microbiology (Feb 2020)
NK Cells Regulate CD8+ T Cell Mediated Autoimmunity
- Philipp A. Lang,
- Philipp A. Lang,
- Philipp A. Lang,
- Sarah Q. Crome,
- Sarah Q. Crome,
- Haifeng C. Xu,
- Haifeng C. Xu,
- Karl S. Lang,
- Karl S. Lang,
- Laurence Chapatte,
- Elissa K. Deenick,
- Elissa K. Deenick,
- Melanie Grusdat,
- Aleksandra A. Pandyra,
- Vitaly I. Pozdeev,
- Ruifeng Wang,
- Tobias A. W. Holderried,
- Tobias A. W. Holderried,
- Harvey Cantor,
- Andreas Diefenbach,
- Andreas Diefenbach,
- Andreas Diefenbach,
- Alisha R. Elford,
- David R. McIlwain,
- Mike Recher,
- Dieter Häussinger,
- Tak W. Mak,
- Tak W. Mak,
- Pamela S. Ohashi,
- Pamela S. Ohashi
Affiliations
- Philipp A. Lang
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Philipp A. Lang
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Philipp A. Lang
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Sarah Q. Crome
- Department of Immunology, University of Toronto, Toronto, ON, Canada
- Sarah Q. Crome
- Toronto General Hospital Research Institute and UHN Transplant, University Health Network, Toronto, ON, Canada
- Haifeng C. Xu
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Haifeng C. Xu
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Karl S. Lang
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Karl S. Lang
- Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Laurence Chapatte
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Elissa K. Deenick
- Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- Elissa K. Deenick
- Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia
- Melanie Grusdat
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Aleksandra A. Pandyra
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Vitaly I. Pozdeev
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Ruifeng Wang
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Tobias A. W. Holderried
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Tobias A. W. Holderried
- Department of Hematology, Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany
- Harvey Cantor
- 0Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Immunology, Harvard Medical School, Boston, MA, United States
- Andreas Diefenbach
- 1Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Andreas Diefenbach
- 2Berlin Institute of Health (BIH), Berlin, Germany
- Andreas Diefenbach
- 3Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany
- Alisha R. Elford
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- David R. McIlwain
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Mike Recher
- 4Medical Outpatient Clinic and Immunodeficiency Lab, University Hospital Basel, Basel, Switzerland
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Tak W. Mak
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Tak W. Mak
- Department of Immunology, University of Toronto, Toronto, ON, Canada
- Pamela S. Ohashi
- Princess Margaret Cancer Centre, Campell Family Institute for Breast Cancer Research, University Health Network (UHN), Toronto, ON, Canada
- Pamela S. Ohashi
- Department of Immunology, University of Toronto, Toronto, ON, Canada
- DOI
- https://doi.org/10.3389/fcimb.2020.00036
- Journal volume & issue
-
Vol. 10
Abstract
Elucidating key factors that regulate immune-mediated pathology in vivo is critical for developing improved strategies to treat autoimmune disease and cancer. NK cells can exhibit regulatory functions against CD8+ T cells following viral infection. Here we show that while low doses of lymphocytic choriomeningitis virus (LCMV-WE) can readily induce strong CD8+ T cell responses and diabetes in mice expressing the LCMV glycoprotein on β-islet cells (RIP-GP mice), hyperglycemia does not occur after infection with higher doses of LCMV. High-dose LCMV infection induced an impaired CD8+ T cell response, which coincided with increased NK cell activity during early time points following infection. Notably, we observed increased NKp46 expression on NK cells during infection with higher doses, which resulted in an NK cell dependent suppression of T cells. Accordingly, depletion with antibodies specific for NK1.1 as well as NKp46 deficiency (Ncr1gfp/gfp mice) could restore CD8+ T cell immunity and permitted the induction of diabetes even following infection of RIP-GP mice with high-dose LCMV. Therefore, we identify conditions where innate lymphoid cells can play a regulatory role and interfere with CD8+ T cell mediated tissue specific pathology using an NKp46 dependent mechanism.
Keywords
