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Pre-Clinical Studies

Proliferation-based T-cell selection for immunotherapy and graft-versus-host-disease prophylaxis in the context of bone marrow transplantation

Bone Marrow Transplantation volume 38, pages 157–167 (2006)Cite this article

Abstract

Graft-versus-host disease (GvHD) caused by alloreactive T cells within the graft is a major drawback of allogeneic BMT, but depletion of T cells leads to higher rates of relapse, opportunistic infections and graft failure. Therefore, selective removal of GvHD-inducing alloreactive T cells might be beneficial. We describe here the separation of alloresponsive T cells, based on carboxyfluorescein succimidyl ester labeling, in vitro allostimulation and FACS-sorting. In vivo effects of the separated cell populations were investigated in the context of allogeneic BMT in murine models: in vitro resting T cells were shown to survive in the allogeneic host and retain immunoreactivity against ‘third-party’ antigens. As demonstrated in two different transplantation models, elimination of proliferating cells significantly reduces GvHD but offers no advantages to using T-cell-depleted bone marrow alone concerning engraftment and tumor control. Transplanting T cells that proliferate in response to tumor antigens in vitro may narrow down the spectrum of antigens recognized by T cells and therefore reduce GvHD while maintaining graft-facilitating function and tumor control. Therefore, selecting tumor-reactive T cells on the basis of their proliferative response in vitro may be beneficial for the recipient, less time consuming than T-cell cloning and still reduce the extent of GvHD.

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Acknowledgements

We thank Dr Christoph Schulte, Department of Pathology for help with cell sorting, Professor P Saftig, Department for Biochemistry for providing lab space and unlimited support of the project, S Gehrmann and T Steffen for technical assistance and Mr Deger for excellent animal care. We are indebted to the DJCLS, Munich, Germany and Deutsche Krebshilfe-Stiftung, Bonn, Germany for financial support. This work is dedicated to Janet and Donald Rowley in gratitude and friendship. This work was supported by Grant R01/07 of the DJCLS, German José Carreras Leukemia Foundation, Munich, Germany and Grant 10-2114, Deutsche Krebshilfe-Stiftung, Bonn, Germany.

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Authors and Affiliations

  1. II Medical Department, University of Kiel, Kiel, Germany

    A Pachnio, S Dietrich, A Humpe, M Gramatzki & C Beck

  2. Department of Pathology, University of Kiel, Kiel, Germany

    W Klapper

  3. Department of Biochemistry, University of Kiel, Kiel, Germany

    M Schwake & R Sedlacek

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Correspondence to C Beck.

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Pachnio, A., Dietrich, S., Klapper, W. et al. Proliferation-based T-cell selection for immunotherapy and graft-versus-host-disease prophylaxis in the context of bone marrow transplantation. Bone Marrow Transplant 38, 157–167 (2006). https://doi.org/10.1038/sj.bmt.1705411

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