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Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection.

Marion RolotAnnette M DougallAlisha ChettyJustine JavauxTing ChenXue XiaoBénédicte MachielsMurray E SelkirkRick M MaizelsCornelis H HokkeOlivier DenisFrank BrombacherAlain VanderplasschenLaurent GilletWilliam G C HorsnellBenjamin G Dewals
Published in: Nature communications (2018)
Infection with parasitic helminths can imprint the immune system to modulate bystander inflammatory processes. Bystander or virtual memory CD8+ T cells (TVM) are non-conventional T cells displaying memory properties that can be generated through responsiveness to interleukin (IL)-4. However, it is not clear if helminth-induced type 2 immunity functionally affects the TVM compartment. Here, we show that helminths expand CD44hiCD62LhiCXCR3hiCD49dlo TVM cells through direct IL-4 signaling in CD8+ T cells. Importantly, helminth-mediated conditioning of TVM cells provided enhanced control of acute respiratory infection with the murid gammaherpesvirus 4 (MuHV-4). This enhanced control of MuHV-4 infection could further be explained by an increase in antigen-specific CD8+ T cell effector responses in the lung and was directly dependent on IL-4 signaling. These results demonstrate that IL-4 during helminth infection can non-specifically condition CD8+ T cells, leading to a subsequently raised antigen-specific CD8+ T cell activation that enhances control of viral infection.
Keyphrases
  • induced apoptosis
  • working memory
  • cell cycle arrest
  • drug induced
  • oxidative stress
  • diabetic rats
  • liver failure
  • immune response
  • hepatitis b virus
  • endothelial cells