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Natural Killer and CD8 T Cells Contribute to Protection by Formalin Inactivated Respiratory Syncytial Virus Vaccination under a CD4-Deficient Condition

  • Eun-Ju Ko (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Youri Lee (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Young-Tae Lee (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Hye Suk Hwang (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Yoonsuh Park (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Ki-Hye Kim (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University) ;
  • Sang-Moo Kang (Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University)
  • Received : 2020.09.03
  • Accepted : 2020.11.02
  • Published : 2020.12.31
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Abstract

Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program to Research Institute for Basic Sciences (RIBS) of Jeju National University through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A1A10072987). This work was also supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) grants AI1093772 (S.M.K).

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