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

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via

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Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DEFINING A TCF1-EXPRESSING PROGENITOR ALLOGENEIC CD8+ T

CELL SUBSET IN ACUTE GRAFT-VERSUS-HOST DISEASE Article Open access 22 September 2023 T CELL EXHAUSTION AND A FAILURE IN ANTIGEN PRESENTATION DRIVE RESISTANCE TO THE GRAFT-VERSUS-LEUKEMIA

EFFECT Article Open access 24 August 2020 ENGINEERED OFF-THE-SHELF THERAPEUTIC T CELLS RESIST HOST IMMUNE REJECTION Article 13 July 2020 REFERENCES * Urbano-Ispizua A, Schmitz N, de Witte T,

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Article  CAS  PubMed  PubMed Central  Google Scholar  Download references 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.

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * II Medical Department, University of Kiel, Kiel, Germany A Pachnio, S Dietrich, A Humpe, M Gramatzki & C Beck * Department of Pathology,

University of Kiel, Kiel, Germany W Klapper * Department of Biochemistry, University of Kiel, Kiel, Germany M Schwake & R Sedlacek Authors * A Pachnio View author publications You can

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Correspondence to C Beck. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 27 July 2005 * Revised: 20 March 2006 * Accepted: 20 April 2006 * Published: 05 July 2006 * Issue Date: 01 July 2006 *

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * T-cell selection * graft-engineering * GvHD *

allogeneic bone marrow transplantation