期刊
PLOS PATHOGENS
卷 13, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006191
关键词
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资金
- Canadian Institutes of Health Research (CIHR) [MOP-133680]
- Alberta Innovates Health Solutions
- Fonds de recherche du Quebec - Sante (FRQS) AIDS and Infectious Disease Network (Reseau SIDA-MI)
- Universite de Montreal
- National CIHR Training Program on Hepatitis C (NCRTP-HepC)
- CIHR
- American Liver Foundation
- Fonds de recherche du Quebec - Sante (FRQS)
- Canadian Network on Hepatitis C (CanHepC)
- Chercheur Boursier salary award from the FRQS
- Alberta Innovates [201201140] Funding Source: researchfish
The dynamics of the memory CD8 T cell receptor (TCR) repertoire upon virus re-exposure and factors governing the selection of TCR clonotypes conferring protective immunity in real life settings are poorly understood. Here, we examined the dynamics and functionality of the virus-specific memory CD8 TCR repertoire before, during and after hepatitis C virus (HCV) reinfection in patients who spontaneously resolved two consecutive infections (SR/SR) and patients who resolved a primary but failed to clear a subsequent infection (SR/CI). The TCR repertoire was narrower prior to reinfection in the SR/SR group as compared to the SR/CI group and became more focused upon reinfection. CD8 T cell clonotypes expanding upon re-exposure and associated with protection from viral persistence were recruited from the memory T cell pool. Individual CD8 T cell lines generated from the SR/SR group exhibited higher functional avidity and polyfunctionality as compared to cell lines from the SR/CI group. Our results suggest that protection from viral persistence upon HCV reinfection is associated with focusing of the HCV-specific CD8 memory T cell repertoire from which established cell lines showed high functional avidity. These findings are applicable to vaccination strategies aiming at shaping the protective human T cell repertoire.
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