Journal article
Bystander Chronic Infection Negatively Impacts Development of CD8(+) T Cell Memory
Immunity (Cambridge, Mass.), v 40(5), pp 801-813
15 May 2014
PMID: 24837104
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Bystander Chronic Infection Negatively Impacts Development of CD8(+) T Cell Memory
- Creators
- Erietta Stelekati - University of PennsylvaniaHaina Shin - University of PennsylvaniaTravis A. Doering - University of PennsylvaniaDouglas V. Dolfi - University of PennsylvaniaCarly G. Ziegler - University of PennsylvaniaDaniel P. Beiting - University of PennsylvaniaLucas Dawson - University of PennsylvaniaJennifer Liboon - University of PennsylvaniaDavid Wolski - Harvard Medical SchoolMohammed-Alkhatim A. Ali - University of PennsylvaniaPeter D. Katsikis - Drexel UniversityHao Shen - University of PennsylvaniaDavid S. Roos - University of PennsylvaniaW. Nicholas Haining - Dana-Farber Cancer InstituteGeorg M. Lauer - Harvard Medical SchoolE. John Wherry - University of Pennsylvania
- Publication Details
- Immunity (Cambridge, Mass.), v 40(5), pp 801-813
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- AI 083022; AI 082630 / NIH/NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) U19AI083022 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000336026100017
- Scopus ID
- 2-s2.0-84900433236
- Other Identifier
- 991019339573604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology