Poster Presentation Lorne Infection and Immunity 2013

Blimp-1 triggers the formation of immunoregulatory IL-10 producing Th1 cells during chronic viral infection (#147)

Ian A Parish 1 2 , Heather D Marshall 1 , Philipp A Lang 3 4 5 , Anne Brüstle 3 , Jonathan H Chen 1 , Weiguo Cui 1 , Pamela S Ohashi 3 4 6 , Casey T Weaver 7 8 , Susan M Kaech 1 9
  1. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
  2. Immunology Department, John Curtin School of Medical Research, Acton, ACT, Australia
  3. Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada
  4. Department of Immunology, University of Toronto, Toronto, ON, Canada
  5. Department of Gastroenterology, Hepatology, and Infectious Diseases, University of Dusseldorf, Dusseldorf, Germany
  6. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
  7. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
  8. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
  9. Howard Hughes Medical Institute,

During many chronic viral infections, the anti-viral T cell response becomes attenuated in a process that is partly host regulated. While elevated expression of the immunosuppressive cytokine IL-10 is involved in this process, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we trace IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection using an IL-10 reporter mouse line. We demonstrate that “exhausted” virus-specific T cells, particularly virus-specific Th1 cells, display elevated IL-10 expression during chronic LCMV infection and that ablation of IL-10 from the T cell compartment can partially restore T cell function and reduce viral loads. We find that Blimp-1 is required for IL-10 expression by Th1 cells and implicate antigen as the likely Blimp-1/IL-10 induction signal. Thus, effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.