Conditioning of naive CD4(+) T cells for enhanced peripheral Foxp3 induction by nonspecific bystander inflammation

Nat Immunol. 2016 Mar;17(3):297-303. doi: 10.1038/ni.3329. Epub 2016 Jan 11.


Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This results in inhibition of immune responses in vivo via a Foxp3-dependent effect on antigen-specific naive CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the idea that early tuning of the immune system by infection affects the long-term quality of immune regulation.

Publication types

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

MeSH terms

  • Animals
  • Asthma / immunology*
  • Autoantigens
  • Autoimmunity / immunology*
  • Bystander Effect / drug effects
  • Bystander Effect / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Cytokines / drug effects
  • Cytokines / immunology*
  • Cytokines / pharmacology
  • DNA Methylation
  • Diabetes Mellitus / immunology*
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Gene Expression Profiling
  • Inflammation*
  • Interferon Inducers / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peripheral Tolerance / immunology
  • Poly I-C / pharmacology
  • Promoter Regions, Genetic
  • Self Tolerance / immunology*


  • Autoantigens
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interferon Inducers
  • thymic stromal lymphopoietin
  • Poly I-C