tetano
Editor, Senior Moderator
PLoS Pathog. 2019 Aug 14;15(8):e1007989. doi: 10.1371/journal.ppat.1007989. eCollection 2019 Aug.
[h=1]Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation.[/h] McKinstry KK[SUP]1[/SUP], Alam F[SUP]1[/SUP], Flores-Malavet V[SUP]1[/SUP], Nagy MZ[SUP]1[/SUP], Sell S[SUP]2[/SUP], Cooper AM[SUP]3[/SUP], Swain SL[SUP]4[/SUP], Strutt TM[SUP]1[/SUP].
[h=3]Author information[/h] 1 Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America. 2 Department of Health, Wadsworth Center, Albany, New York, United States of America. 3 Trudeau Institute, Saranac Lake, New York, United States of America. 4 Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
[h=3]Abstract[/h] Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.
PMID: 31412088 DOI: 10.1371/journal.ppat.1007989
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[h=1]Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation.[/h] McKinstry KK[SUP]1[/SUP], Alam F[SUP]1[/SUP], Flores-Malavet V[SUP]1[/SUP], Nagy MZ[SUP]1[/SUP], Sell S[SUP]2[/SUP], Cooper AM[SUP]3[/SUP], Swain SL[SUP]4[/SUP], Strutt TM[SUP]1[/SUP].
[h=3]Author information[/h] 1 Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America. 2 Department of Health, Wadsworth Center, Albany, New York, United States of America. 3 Trudeau Institute, Saranac Lake, New York, United States of America. 4 Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
[h=3]Abstract[/h] Defining the most penetrating correlates of protective memory T cells is key for designing improved vaccines and T cell therapies. Here, we evaluate how interleukin (IL-2) production by memory CD4 T cells, a widely held indicator of their protective potential, impacts immune responses against murine influenza A virus (IAV). Unexpectedly, we show that IL-2-deficient memory CD4 T cells are more effective on a per cell basis at combating IAV than wild-type memory cells that produce IL-2. Improved outcomes orchestrated by IL-2-deficient cells include reduced weight loss and improved respiratory function that correlate with reduced levels of a broad array of inflammatory factors in the infected lung. Blocking CD70-CD27 signals to reduce CD4 T cell IL-2 production tempers the inflammation induced by wild-type memory CD4 T cells and improves the outcome of IAV infection in vaccinated mice. Finally, we show that IL-2 administration drives rapid and extremely potent lung inflammation involving NK cells, which can synergize with sublethal IAV infection to promote acute death. These results suggest that IL-2 production is not necessarily an indicator of protective CD4 T cells, and that the lung environment is particularly sensitive to IL-2-induced inflammation during viral infection.
PMID: 31412088 DOI: 10.1371/journal.ppat.1007989
Free full text