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

Research output: Contribution to journalArticlepeer-review


  • Marion Rolot
  • Annette M Dougall
  • Alisha Chetty
  • Justine Javaux
  • Ting Chen
  • Xue Xiao
  • Bénédicte Machiels
  • Murray E Selkirk
  • Rick M Maizels
  • Cornelis Hokke
  • Olivier Denis
  • Frank Brombacher
  • Alain Vanderplasschen
  • Laurent Gillet
  • Benjamin G Dewals

Colleges, School and Institutes

External organisations

  • Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.


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.


Original languageEnglish
Article number4516
Number of pages16
JournalNature Communications
Issue number1
Early online date30 Oct 2018
Publication statusPublished - Dec 2018