Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans

Natalia Izotova, Christine Rivat, Cristina Baricordi, Elena Blanco, Danilo Pellin, Eleanor Watt, Athina S. Gkazi, Stuart Adams, Kimberly Gilmour, Jinhua Bayford, Claire Booth, H. Bobby Gaspar, Adrian J. Thrasher () and Luca Biasco ()
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Natalia Izotova: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Christine Rivat: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Cristina Baricordi: Harvard Medical School
Elena Blanco: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Danilo Pellin: Harvard Medical School
Eleanor Watt: Great Ormond Street Hospital
Athina S. Gkazi: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Stuart Adams: Great Ormond Street Hospital
Kimberly Gilmour: Great Ormond Street Hospital
Jinhua Bayford: Great Ormond Street Hospital
Claire Booth: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
H. Bobby Gaspar: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Adrian J. Thrasher: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences
Luca Biasco: Great Ormond Street Institute of Child Health Faculty of Population Health Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21834-9

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DOI: 10.1038/s41467-021-21834-9

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