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Lymphoma

T-cell receptor diversity prevents T-cell lymphoma development

Leukemia volume 26, pages 2499–2507 (2012)Cite this article

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Abstract

Mature T-cell lymphomas (MTCLs) have an extremely poor prognosis and are much less frequent than immature T-cell leukemias. This suggests that malignant outgrowth of mature T lymphocytes is well controlled. Indeed, in a previous study we found that mature T cells are resistant to transformation with known T-cell oncogenes. Here, however, we observed that T-cell receptor (TCR) mono-/oligoclonal mature T cells from TCR transgenic (tg) mice (OT-I, P14) expressing the oncogenes NPM/ALK or ΔTrkA readily developed MTCLs in T-cell-deficient recipients. Analysis of cell surface markers largely ruled out that TCR tg lymphomas were derived from T-cell precursors. Furthermore, cotransplanted non-modified TCR polyclonal T cells suppressed malignant outgrowth of oncogene expressing TCR tg T lymphocytes. A dominant role of an anti-leukemic immune response or Tregs in the control of MTCLs seems unlikely as naïve T cells derived from oncogene expressing stem cells, which should be tolerant to leukemic antigens, as well as purified CD4 and CD8 were resistant to transformation. However, our results are in line with a model in which homeostatic mechanisms that stabilize the diversity of the normal T-cell repertoire, for example, clonal competition, also control the outgrowth of potentially malignant T-cell clones. This study introduces a new innate mechanism of lymphoma control.

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Acknowledgements

NG was supported by a scholarship of Merck Serono within the Graduiertenkolleg GRK1172 of the Deutsche Forschungs-gemeinschaft. Furthermore, the study was funded by the Deutsche Forschungs-gemeinschaft (LA1135/9-1) within the SPP1230. We thank Ekaterini Hadzoglou and Robin Wistinghausen for their excellent technical assistance. We also thank Felix Hermann, Jörg Kirberg and Ralf Küppers for the highly valuable discussions of the presented data.

AUTHOR CONTRIBUTIONS

SN designed experiments, performed research, analyzed data and wrote the paper. TH performed research, analyzed data and edited the paper. NAG, MP, BR and AK performed research. HMJ performed Ig-rearrangement analysis, SH and MLH performed histological analyses, SG and IR performed the statistical analyses. DVL designed experiments, analyzed data and wrote the paper.

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Author notes

  1. N Al-Ghaili and T Heinrich: These authors contributed equally to this work.

Authors and Affiliations

  1. Senckenberg Institute of Pathology, Goethe-University Hospital, Frankfurt am Main, Germany

    S Newrzela, T Heinrich, M Petkova, S Hartmann, B Rengstl & M-L Hansmann

  2. Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main, Germany

    N Al-Ghaili & A Kumar

  3. Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Erlangen, Germany

    H-M Jäck

  4. Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

    S Gerdes & I Roeder

  5. Institute of Virology, Innsbruck Medical University, Innsbruck, Austria

    D von Laer

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  1. S Newrzela
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Correspondence to D von Laer.

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Newrzela, S., Al-Ghaili, N., Heinrich, T. et al. T-cell receptor diversity prevents T-cell lymphoma development. Leukemia 26, 2499–2507 (2012). https://doi.org/10.1038/leu.2012.142

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