Crossreactive influenza A(IAV)-Specific CD4 memory cells enhance viral load during lymphocytic choriomeningitis (LCMV) infection (IRC5P.635)
  • Liisa Selin,
  • Priti Agarwal,
  • Anke Kraft,
  • and Myriam Wlodarczyk

J Immunol 2015 194:58.18 Abstract

IAV is a common human respiratory pathogen with a strong association with heterotypic and heterologous immunity. IAV-immune mice challenged with LCMV develop detrimental effects with both increased virus titers and immunopathology. Crossreactive CD8 T cell responses between these two viruses mediate the enhanced lung pathology. Here, we questioned whether crossreactive CD4 memory cells in IAV-immune mice could play a role in increasing viral titers during the subsequent LCMV infection. Preferential depletion of memory CD4 but not CD8 cells in IAV-immune mice prevented the increase in LCMV titers. In IAV+LCMV mice there was an early increase in CD4 cells with a shift in the CD4/CD8 ratio. Luminex cytokine assays suggested that there was an increase in Th2 cytokines, IL-4 and IL-5, in the spleen of IAV+LCMV mice, which was IAV CD4 memory cell dependent, as IL-4 decreased in the CD4 depleted mice. Depleting IL-4 or IL-5 returned LCMV titers to nave levels while adding rIL-4 and rIL-5 together to nave mice increased virus titers. This suggests that the crossreactive heterologous response was more Th2-polarized and that since memory cytokines are produced early they may shift the normally strong Th1-type response to LCMV towards a more Th2-type response, inhibiting appropriate CD8 activation and impeding viral clearance. This shift to stronger Th2-type response would contribute to detrimental effects as LCMV requires a strong CD8 response and perforin to clear.
  • Copyright 2015 by The American Association of Immunologists, Inc.