Chronic virus infection compromises memory bystander T cell function in an IL-6/STAT1-dependent manner

Autor: Annette Oxenius, Nicole Joller, Nicolas S. Baumann, Alexander Yermanos, Mariana Borsa, Roman Spörri, Nike Julia Krautler, Suzanne P. M. Welten, Katharina Pallmer, Isabel Barnstorf
Přispěvatelé: University of Zurich
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
T-Lymphocytes
viruses
CD8-Positive T-Lymphocytes
10263 Institute of Experimental Immunology
0302 clinical medicine
Bystander effect
Cytotoxic T cell
Immunology and Allergy
Lymphocytic choriomeningitis virus
Receptors
Immunologic
Research Articles
Mice
Knockout
3. Good health
medicine.anatomical_structure
STAT1 Transcription Factor
Virus Diseases
Host-Pathogen Interactions
2723 Immunology and Allergy
Female
T cell
Immunology
Context (language use)
610 Medicine & health
Mice
Transgenic
Lymphocytic Choriomeningitis
News
Infections
Insights
Virus
Article
03 medical and health sciences
Immunity
medicine
Humans
Animals
Lectins
C-Type
2403 Immunology
business.industry
Interleukin-6
Perforin
Bystander Effect
Mice
Inbred C57BL
Chronic infection
030104 developmental biology
Chronic Disease
570 Life sciences
biology
business
Immunologic Memory
CD8
030215 immunology
Zdroj: Journal of Experimental Medicine, 216 (3)
The Journal of Experimental Medicine
Popis: Barnstorf et al. demonstrate that chronic viral infections numerically reduce memory non–virus-specific (bystander) cytotoxic T lymphocytes and alter their phenotype and function. Phenotypic changes are induced by the inflammatory cytokine IL-6, and functional impairment is not cell-intrinsic but inferred by the chronically infected host.
Chronic viral infections are widespread among humans, with ∼8–12 chronic viral infections per individual, and there is epidemiological proof that these impair heterologous immunity. We studied the impact of chronic LCMV infection on the phenotype and function of memory bystander CD8+ T cells. Active chronic LCMV infection had a profound effect on total numbers, phenotype, and function of memory bystander T cells in mice. The phenotypic changes included up-regulation of markers commonly associated with effector and exhausted cells and were induced by IL-6 in a STAT1-dependent manner in the context of chronic virus infection. Furthermore, bystander CD8 T cell functions were reduced with respect to their ability to produce inflammatory cytokines and to undergo secondary expansion upon cognate antigen challenge with major cell-extrinsic contributions responsible for the diminished memory potential of bystander CD8+ T cells. These findings open new perspectives for immunity and vaccination during chronic viral infections.
Graphical Abstract
Databáze: OpenAIRE
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