Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance
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 T...
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| Veröffentlicht in: | PLoS pathogens 2017-02, Vol.13 (2), p.e1006191-e1006191 |
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| creator | Abdel-Hakeem, Mohamed S Boisvert, Maude Bruneau, Julie Soudeyns, Hugo Shoukry, Naglaa H |
| description | 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. |
| doi_str_mv | 10.1371/journal.ppat.1006191 |
| format | Article |
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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. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Abdel-Hakeem MS, Boisvert M, Bruneau J, Soudeyns H, Shoukry NH (2017) Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance. PLoS Pathog 13(2): e1006191. doi:10.1371/journal.ppat.1006191</rights><rights>2017 Abdel-Hakeem et al 2017 Abdel-Hakeem et al</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Abdel-Hakeem MS, Boisvert M, Bruneau J, Soudeyns H, Shoukry NH (2017) Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28146579</pmid><doi>10.1371/journal.ppat.1006191</doi><orcidid>https://orcid.org/0000-0001-9304-7796</orcidid><orcidid>https://orcid.org/0000-0001-5857-3176</orcidid><orcidid>https://orcid.org/0000-0002-8817-8238</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bacterial infections Biology and Life Sciences CD8 lymphocytes CD8-Positive T-Lymphocytes - immunology Comparative analysis Expansion Flow Cytometry Funding Health aspects Hepacivirus - immunology Hepatitis Hepatitis C - immunology Hepatitis C virus Humans Immunologic Memory - immunology Infections Lymphocytes Medicine and Health Sciences Patients Peptides Physiological aspects Prevention Receptors, Antigen, T-Cell, alpha-beta - immunology Research and Analysis Methods Risk factors T cell receptors Viral infections |
| title | Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance |
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