Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance

被引：28

作者：

Abdel-Hakeem, Mohamed S. ^{[1
,2
,3
]}

Boisvert, Maude ^{[1
]}

Bruneau, Julie ^{[1
,4
]}

Soudeyns, Hugo ^{[3
,5
]}

Shoukry, Naglaa H. ^{[1
,6
]}

机构：

[1] Univ Montreal CRCHUM, Ctr Hosp, Ctr Rech, Montreal, PQ H3C 3J7, Canada

[2] Cairo Univ, Fac Pharm, Dept Microbiol & Immunol, Cairo, Egypt

[3] Univ Montreal, Dept Microbiol & Immunol, Dept Infectiol & Immunol, Montreal, PQ H3C 3J7, Canada

[4] Univ Montreal, Dept Med Familiale & Med Urgenc, Montreal, PQ H3C 3J7, Canada

[5] Univ Sainte Justine, Ctr Hosp, Montreal, PQ, Canada

[6] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

来源：

PLOS PATHOGENS | 2017年 / 13卷 / 02期

基金：

加拿大健康研究院;

关键词：

ANTIGEN-SENSITIVITY; RECEPTOR REPERTOIRE; CROSS-REACTIVITY; VIRAL-INFECTION; HIV CONTROL; RESPONSES; DIVERSITY; ESCAPE; HCV; DETERMINANTS;

D O I：

10.1371/journal.ppat.1006191

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：25

共 54 条

[1] Signatures of Protective Memory Immune Responses During Hepatitis C Virus Reinfection [J].

Abdel-Hakeem, Mohamed S. ;

Bedard, Nathalie ;

Murphy, Donald ;

Bruneau, Julie ;

Shoukry, Naglaa H. .

GASTROENTEROLOGY, 2014, 147 (04) :870-U261

[2] Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover [J].

Almeida, Jorge R. ;

Price, David A. ;

Papagno, Laura ;

Arkoub, Zaina Ait ;

Sauce, Delphine ;

Bornstein, Ethan ;

Asher, Tedi E. ;

Samri, Assia ;

Schnuriger, Aurelie ;

Theodorou, Ioannis ;

Costagliola, Dominique ;

Rouzioux, Christine ;

Agut, Henri ;

Marcelin, Anne-Genevieve ;

Douek, Daniel ;

Autran, Brigitte ;

Appay, Victor .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (10) :2473-2485

[3] Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity [J].

Almeida, Jorge R. ;

Sauce, Delphine ;

Price, David A. ;

Papagno, Laura ;

Shin, So Youn ;

Moris, Arnaud ;

Larsen, Martin ;

Pancino, Gianfranco ;

Douek, Daniel C. ;

Autran, Brigitte ;

Saez-Cirion, Asier ;

Appay, Victor .

BLOOD, 2009, 113 (25) :6351-6360

[4]

Ando K, 1997, J IMMUNOL, V158, P5283

[5] Antigen sensitivity and T-cell receptor avidity as critical determinants of HIV control [J].

Appay, Victor ;

Iglesias, Maria C. .

CURRENT OPINION IN HIV AND AIDS, 2011, 6 (03) :157-162

[6] Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells [J].

Badr, Gamal ;

Bedard, Nathalie ;

Abdel-Hakeem, Mohamed S. ;

Trautmann, Lydie ;

Willems, Bernard ;

Villeneuve, Jean-Pierre ;

Haddad, Elias K. ;

Sekaly, Rafick P. ;

Bruneau, Julie ;

Shoukry, Naglaa H. .

JOURNAL OF VIROLOGY, 2008, 82 (20) :10017-10031

[7] Public T cell receptors confer high-avidity CD4 responses to HIV controllers [J].

Benati, Daniela ;

Galperin, Moran ;

Lambotte, Olivier ;

Gras, Stephanie ;

Lim, Annick ;

Mukhopadhyay, Madhura ;

Nouel, Alexandre ;

Campbell, Kristy-Anne ;

Lemercier, Brigitte ;

Claireaux, Mathieu ;

Hendou, Samia ;

Lechat, Pierre ;

de Truchis, Pierre ;

Boufassa, Faroudy ;

Rossjohn, Jamie ;

Delfraissy, Jean-Francois ;

Arenzana-Seisdedos, Fernando ;

Chakrabarti, Lisa A. .

JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (06) :2093-2108

[8] High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control [J].

Berger, Christoph T. ;

Frahm, Nicole ;

Price, David A. ;

Mothe, Beatriz ;

Ghebremichael, Musie ;

Hartman, Kari L. ;

Henry, Leah M. ;

Brenchley, Jason M. ;

Ruff, Laura E. ;

Venturi, Vanessa ;

Pereyra, Florencia ;

Sidney, John ;

Sette, Alessandro ;

Douek, Daniel C. ;

Walker, Bruce D. ;

Kaufmann, Daniel E. ;

Brander, Christian .

JOURNAL OF VIROLOGY, 2011, 85 (18) :9334-9345

[9] The narrowing of the CD8 T cell repertoire in old age [J].

Blackman, Marcia A. ;

Woodland, David L. .

CURRENT OPINION IN IMMUNOLOGY, 2011, 23 (04) :537-542

[10] Evolution of the T cell repertoire during primary, memory, and recall responses to viral infection [J].

Blattman, JN ;

Sourdive, DJD ;

Murali-Krishna, K ;

Ahmed, R ;

Altman, JD .

JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6081-6090

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