Bystander chronic infection negatively impacts development of CD8(+) T cell memory

Immunity. 2014 May 15;40(5):801-13. doi: 10.1016/j.immuni.2014.04.010.


Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8(+) T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8(+) T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8(+) T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bacterial Infections / immunology*
  • Bystander Effect / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Chronic Disease
  • Humans
  • Immunologic Memory / immunology*
  • Inflammation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1
  • T-Box Domain Proteins / immunology
  • Transcription Factors / immunology
  • Virus Diseases / immunology*


  • Prdm1 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1