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Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection

Nature Immunology volume 18, pages 393401 (2017) | Download Citation

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To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private. In patients undergoing HSC transplantation, γδ T cells were quickly reconstituted; however, they had profoundly altered TCR repertoires. Notably, the clonal proliferation of individual virus-reactive γδ TCR sequences in patients with reactivation of cytomegalovirus revealed strong evidence for adaptive anti-viral γδ T cell immune responses.

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  • 14 February 2018

    In the version of this Article originally published, in Acknowledgments section "Deutsche José Carreras Leukämie-Stiftung e.V. (DJCLS R12/29 to C.K. and I.P.)", text were missing. The text has been included in PDF and XML. These have been corrected after print.


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We thank E. Hage and T. Schulz for assistance from the central project Z1, an NGS core facility of Collaborative Research Centre SFB900; C. Struckmann and M. Ballmaier for technical guidance and single-cell sorting; the Hannover Unified Biobank of Hannover Medical School; A. Krueger for reading and criticizing the manuscript; and J. Blume for help in cord-blood preparation. Supported by Deutsche Forschungsgemeinschaft, (SFB900/B8 to C.K. and I.P.), Deutsche José Carreras Leukämie-Stiftung e.V. (DJCLS R12/29 to C.K. and I.P.) and PR727/4-1 to I.P.) and the German Federal Ministry of Education and Research (01EO1302 to C.S.-F., C.K. and I.P.).

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Author notes

    • Christian Koenecke
    •  & Immo Prinz

    These authors contributed equally to this work.


  1. Institute of Immunology, Hannover Medical School, Hannover, Germany.

    • Sarina Ravens
    • , Christian Schultze-Florey
    • , Solaiman Raha
    • , Inga Sandrock
    • , Linda Oberdörfer
    • , Annika Reinhardt
    • , Inga Ravens
    • , Maleen Beck
    • , Reinhold Förster
    • , Christian Koenecke
    •  & Immo Prinz
  2. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

    • Christian Schultze-Florey
    • , Melanie Drenker
    • , Maleen Beck
    • , Michael Heuser
    • , Felicitas Thol
    • , Arnold Ganser
    •  & Christian Koenecke
  3. Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.

    • Christian Schultze-Florey
    • , Christian Koenecke
    •  & Immo Prinz
  4. Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.

    • Robert Geffers
  5. Department Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical School, Hannover, Germany.

    • Constantin von Kaisenberg


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Sa.R. wrote the manuscript; Sa.R., C.S.-F. and So.R. designed and performed experiments, discussed and analyzed data; I.S., A.R., I.R. and M.B. helped with performing experiments and data analysis; M.D. and L.O. organized, acquired and processed clinical samples; R.G., M.H. and F.T. helped supervise NGS; C.v.K. and A.G. helped supervise clinical sample acquisition; R.F. helped supervise research; C.K. supervised research and the clinical study, and discussed and analyzed data; and I.P. supervised research, discussed and analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Immo Prinz.

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