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In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping

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Abstract

Myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DCleu) regaining the stimulatory capacity of professional DCs while presenting the leukemic antigen repertoire. But so far, the induced antileukemic T-cell responses are variable both in specificity and in efficacy. In an attempt to elucidate the underlying causes of different T-cell response patterns, T-cell receptor (TR) Vβ chain rearrangements were correlated with the T cells corresponding immunophenotypic profile, as well as their proliferative response and cytolytic capacities. In three different settings, donor T cells, either human leukocyte antigen matched or mismatched (haploidentical), or autologous T cells were repeatedly stimulated with myeloid blasts or leukemia-derived DC/DCleus from the corresponding patients diseased from acute myeloid leukemia (AML). Although no significant differences in T-cell proliferation were observed, the T-cell-mediated cytolytic response pattern varied considerably and even caused blast proliferation in two cases. Spectratyping revealed a remarkable restriction (>75 % of normal level) of the CD4+ or CD8+-TR repertoire of blast- or DC/DCleu-stimulated T cells. Although in absolute terms, DC/DCleu stimulation induced the highest grade of restriction in the CD8+ T-cell subset, the CD4+ T-cell compartment seemed to be relatively more affected. But most importantly, in vitro stimulation with DC/DCleu resulted into an identical TR restriction pattern (β chain) that could be identified in vivo in a patient sample 3 months after allo-SCT. Thus, in vitro tests combining functional flow cytometry with spectratyping might provide predictive information about T cellular response patterns in vivo.

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Acknowledgments

This work was supported by grants of the Deutsche Forschungsgesellschaft (SFB/TR 36) to Hans-Jochem Kolb, Susanne Reuther and Arndt Borkhardt; R. Buhmann was supported by grants of the EU (Stemdiagnostics/LSHB-CT-2007037703). We are indebted to many nurses and physicians for their unconditional assistance in patient care, referral of patient material and data collection. For extended bioinformatic assistance, we are cordially indebted to Jens Stoye and Nils Hoffmann. Parts of the results presented in this manuscript were worked out in the doctoral thesis of Susanne Reuther.

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Authors and Affiliations

  1. Faculty of Medical, Department of Paediatric Oncology, Haematology and Immunology, University Dusseldorf, 40225, Dusseldorf, Germany

    Susanne Reuther, Friedhelm R. Schuster, Pina Krell & Arndt Borkhardt

  2. Department of Medicine III, University of Munich-Grosshadern, Munich, Germany

    Helga Schmetzer, Christine Grabrucker, Anja Liepert, Tanja Kroell, Hans-Jochem Kolb & Raymund Buhmann

  3. Helmholtz Center Munich, German Research Center for Environmental Health, CCG-HCT, Marchioninistr. 25, 81377, Munich, Germany

    Hans-Jochem Kolb & Raymund Buhmann

  4. Faculty of Technology and Institute for Bioinformatics, Center for Biotechnology, Bielefeld University, Bielefeld, Germany

    Pina Krell

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  1. Susanne Reuther
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  2. Helga Schmetzer
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  3. Friedhelm R. Schuster
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Correspondence to Raymund Buhmann.

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Susanne Reuther, Helga Schmetzer, Friedhelm R. Schuster contributed equally.

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Reuther, S., Schmetzer, H., Schuster, F.R. et al. In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping. Clin Exp Med 13, 29–48 (2013). https://doi.org/10.1007/s10238-012-0180-y

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  • DOI: https://doi.org/10.1007/s10238-012-0180-y

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