Identification of human progenitors of exhausted CD8 T cells associated with elevated IFN-γ response in early phase of viral infection

C Cai; J Samir; MR Pirozyan; TN Adikari; M Gupta; P Leung; B Hughes; W Van der Byl; S Rizzetto; A Elthala; E Keoshkerian; JL Palgen; T Peters; THO Nguyen; R Louie; K Kedzierska; S Gaudieri; RA Bull; AR Lloyd; F Luciani

Journal article

Identification of human progenitors of exhausted CD8 T cells associated with elevated IFN-γ response in early phase of viral infection

C Cai, J Samir, MR Pirozyan, TN Adikari, M Gupta, P Leung, B Hughes, W Van der Byl, S Rizzetto, A Elthala, E Keoshkerian, JL Palgen, T Peters, THO Nguyen, R Louie, K Kedzierska, S Gaudieri, RA Bull, AR Lloyd, F Luciani

Nature Communications | NATURE PORTFOLIO | Published : 2022

DOI: 10.1038/s41467-022-35281-7

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Abstract

T cell exhaustion is a hallmark of hepatitis C virus (HCV) infection and limits protective immunity in chronic viral infections and cancer. Limited knowledge exists of the initial viral and immune dynamics that characterise exhaustion in humans. We studied longitudinal blood samples from a unique cohort of individuals with primary infection using single-cell multi-omics to identify the functions and phenotypes of HCV-specific CD8+ T cells. Early elevated IFN-γ response against the transmitted virus is associated with the rate of immune escape, larger clonal expansion, and early onset of exhaustion. Irrespective of disease outcome, we find heterogeneous subsets of progenitors of exhaustion, b..

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University of Melbourne Researchers

Oanh Nguyen Author

Katherine Kedzierska Author

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NOVEL BIOINFORMATIC METHODS TO DETERMINE THE LINK BETWEEN GENOMIC COMPLEXITY OF HEPATITIS VIRUSES AND LIVER DISEASE PHENOTYPES

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

The HITS-p and HITS-c investigators include Andrew Lloyd, Lisa Maher, Kate Dolan, Paul Haber, William Rawlinson, Carla Treloar and Greg Dore. Flow cytometry and sequencing were supported by staff at the UNSW Flow Cytometry and Ramaciotti Centre core facilities. This research was supported from National Health and Medical Research Council of Australia (NHMRC) -Project Nos. APP1121643, 1027551, 1060199, Partnership No. 1016351, and Programme Nos. 510488 and 1053206. The HITS-c cohort was supported by the UNSW Hepatitis C Vaccine Initiative and NHMRC Project Grant No. 630483. F.L., A.R.L. and R.A.B. are supported by NHMRC Research Fellowships (Numbers: 1128416, 1041897 and 1084706). M.R.P., P.L., and C.C. were supported by an Australian Government Research Training Programme (RTP) Scholarship. S.G. was supported by the NHMRC grant APP1148284. K.K. is supported by the NHMRC grant APP1148284. Leadership Investigator Grant (#1173871), T.H.O.N. is supported by NHMRC Emerging Leadership Level 1 Investigator Grant (#1194036).