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Post-transplant Events

T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft

Bone Marrow Transplantation volume 45, pages 325–331 (2010)Cite this article

Abstract

In addition to its established hematological indications, autologous hematopoietic SCT (HSCT) can ameliorate the course of severe autoimmune disorders through a reconditioning of the immune system. We have shown earlier that HSCT determines extensive renewal of the TCR repertoire in multiple sclerosis patients. However, the observed persistence post-therapy of some pre-existing T-cell clones suggested the potential for disease recapitulation. Here, we investigated whether TCRs that reappear after a myeloablative conditioning regimen and HSCT were reintroduced with the autologous, CD34-selected hematopoietic stem cell (HSC) graft. In all, we cloned and sequenced 2237 TCR clones from peripheral blood and HSC grafts from four patients who underwent autologous HSCT for severe multiple sclerosis. Surprisingly, in-frame TCR sequences were detectable in only one of four patient grafts and no TCR sequences were found to be shared between the graft and pre- or post-HSCT samples. These findings provide the first evidence from extensive sequencing analysis to suggest that T cells in autologous HSC grafts that have been mobilized with CY+G-CSF and CD34-selected have limited survival capacity and are therefore unlikely to be a major source of carryover of T-cell expansions potentially involved in autoimmune disease.

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Acknowledgements

We thank JW Nagle and D Kauffman (NINDS DNA sequencing facility) for the outstanding sequencing support, and D Carassiti for technical assistance. We also thank D Douek for helpful suggestions and for providing oligonucleotide primers, and S Gagnon and B Biddison for providing the plasmids, Q334 and F6. This work was supported by the intramural NINDS program of the National Institutes of Health (AND, RM, PAM). PAM is also grateful for support from the NIHR Biomedical Research Centre funding scheme and the Hammersmith Hospital Research Trustees Committee (Ref. No. 70159).

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Authors and Affiliations

  1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    A N Dubinsky, R Martin & P A Muraro

  2. Division of Neuroscience and Mental Health, Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK

    A N Dubinsky & P A Muraro

  3. Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    R K Burt

  4. Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, Hamburg, Germany

    R Martin

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  1. A N Dubinsky
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Correspondence to P A Muraro.

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Dubinsky, A., Burt, R., Martin, R. et al. T-cell clones persisting in the circulation after autologous hematopoietic SCT are undetectable in the peripheral CD34+ selected graft. Bone Marrow Transplant 45, 325–331 (2010). https://doi.org/10.1038/bmt.2009.139

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