1. Bystander Chronic Infection Negatively Impacts Development of CD8+ T Cell Memory
- Author
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Travis A. Doering, David Wolski, Daniel P. Beiting, Erietta Stelekati, Lucas Dawson, Douglas V. Dolfi, Hao Shen, Carly G. K. Ziegler, Jennifer Liboon, Georg M. Lauer, E. John Wherry, David S. Roos, W. Nicholas Haining, Mohammed Alkhatim A. Ali, Peter D. Katsikis, and Haina Shin
- Subjects
Immunology ,Priming (immunology) ,Inflammation ,Biology ,CD8-Positive T-Lymphocytes ,Article ,Mice ,Immune system ,Immunity ,medicine ,Bystander effect ,Cytotoxic T cell ,Animals ,Humans ,Immunology and Allergy ,Mice, Knockout ,Cell Differentiation ,Bacterial Infections ,Bystander Effect ,Adoptive Transfer ,3. Good health ,Mice, Inbred C57BL ,Chronic infection ,Infectious Diseases ,Virus Diseases ,Chronic Disease ,Positive Regulatory Domain I-Binding Factor 1 ,medicine.symptom ,T-Box Domain Proteins ,Immunologic Memory ,CD8 ,Transcription Factors - Abstract
SummaryEpidemiological 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.
- Published
- 2014
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