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

Nat Commun. 2018 Oct 30;9(1):4516. doi: 10.1038/s41467-018-06978-5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cricetinae
  • Herpesviridae Infections / immunology*
  • Immunologic Memory / immunology*
  • Interleukin-4 / immunology*
  • Mice
  • Respiratory Tract Infections / immunology*
  • Rhadinovirus
  • Schistosoma mansoni
  • Schistosomiasis mansoni / immunology*
  • Tumor Virus Infections / immunology*


  • Interleukin-4