Journal article

Clonally diverse CD38( )HLA-DR( )CD8( ) T cells persist during fatal H7N9 disease

Zhongfang Wang, Lingyan Zhu, Thi HO Nguyen, Yanmin Wan, Sneha Sant, Sergio M Quinones-Parra, Jeremy Chase Crawford, Auda A Eltahla, Simone Rizzetto, Rowena A Bull, Chenli Qiu, Marios Koutsakos, E Bridie Clemens, Liyen Loh, Tianyue Chen, Lu Liu, Pengxing Cao, Yanqin Ren, Lukasz Kedzierski, Tom Kotsimbos Show all



Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8+ T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38+HLA-DR+PD-1+ CD8+ T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by sing..

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Awarded by NSFC

Awarded by Program for Emergency Response to H7N9 Outbreak

Awarded by 973 National Key Basic Research Project

Awarded by NHMRC Program

Funding Acknowledgements

We thank Janine Roney, Leah Christie, Jill Garlick for patient recruitment (Alfred Hospital), and Nicola Bird for technical assistance. This work was supported by NSFC 81471556, 81470094, 81430030, 81672018, Program for Emergency Response to H7N9 Outbreak (2013QLG003), Shanghai Municipal Commission of Health and Family Planning, and the 973 National Key Basic Research Project (2014CB542502), Ministry of Science and Technology of P.R. China, the University of Melbourne IRRTF Grant, and an NHMRC Program Grant (1071916) to K.K., N.L.L.G., S.J.T., and P.C.D. Z.W. was an NHMRC China-Australia Exchange Fellow, E.B.C., and A.A.E. are NHMRC Peter Doherty Fellows, F.L. is an NHMRC Career Development Fellow Level 2 Fellow, S.J.T. is an NHMRC Principal Research Fellow and K.K. is an NHMRC SRF Level B Fellow. S.Q. P. was a recipient of the University of Melbourne International Research Scholarship and a CONACyT Scholar. S.S. is supported by the Victoria-India Doctoral Scholarship (VIDS) and Melbourne International Fee Remission Scholarship (MIFRS). M.K. is a recipient of Melbourne International Research Scholarship and MIFRS. A.C. is supported by a NHMRC Career Development Fellowship.