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Interleukin-15 deficiency promotes the development of T-cell acute lymphoblastic leukemia in non-obese diabetes mice with severe combined immunodeficiency

Leukemia volume 30, pages 1749–1752 (2016)Cite this article

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Adoptively transferred splenocytes from 8.3-NOD donors populate the lymphoid organs of NOD/SCID recipients with CD8+ and CD4+ T cells, which express the transgenic 8.3-TCR (Figure 1d, upper panels). In contrast, leukemic cells accumulating in NOD/SCID.Il15−/− mice showed CD4hiCD8lo phenotype and did not express the 8.3-TCR (Figure 1d, lower panels), suggesting that the IL-15-deficient lymphopenic environment in NOD/SCID.Il15−/− mice gave rise to abnormal CD4+CD8loTCR− cells with leukemic properties. To test whether these leukemic cells outnumbered autoreactive CD8+ T cells, the leukemic cells were adoptively transferred to NOD/SCID mice along with splenocytes from diabetic NOD donors (Supplementary Figure S2a). The leukemic cells not only prevented type 1 diabetes in NOD/SCID recipients but also expanded robustly, causing lymphadenopathy, splenomegaly, kidney enlargement and death within 4–6 weeks (Supplementary Figure S2b). The expanding cells retained the CD4+CD8int phenotype, expressed CD5 but not major histocompatibility complex-I or B220 (Supplementary Figure S3). These observations indicated that the leukemic cells outnumbered the diabetogenic CD8+ T cells and retained aggressive growth potential even in an IL-15-sufficient environment.

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Acknowledgements

This work was supported by NSERC Discovery grants to SI and SR. We thank Dr Josée Lamoureux for technical assistance. DB is a recipient of a postdoctoral fellowship from Fonds de Recherché du Québec-Santé (FRQS). CR-CHUS is an FRQS-funded research center.

Author contributions

DB, JY, SR and SI designed the experiments, analyzed and interpreted data, and wrote the manuscript. DB, EB and XLC performed the experiments. RK and MM assisted in performing the experiments. HK and FB participated in data analysis and in writing the manuscript.

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Author notes

  1. S Ramanathan and S Ilangumaran: SR and SI share senior authorship.

Authors and Affiliations

  1. Immunology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada

    D Bobbala, R Kandhi, X Chen, M Mayhue, S Ramanathan & S Ilangumaran

  2. Genetics Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada

    E Bouchard & J Yan

  3. Department of Hematology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada

    H Knecht

  4. Department of Medicine, Université Laval, Quebec City, QC, Canada

    F Barabé

  5. CHU de Québec-Université Laval, Quebec City, QC, Canada

    F Barabé

  6. CR-CHUS, Sherbrooke, Québec, Canada

    S Ramanathan & S Ilangumaran

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Bobbala, D., Kandhi, R., Chen, X. et al. Interleukin-15 deficiency promotes the development of T-cell acute lymphoblastic leukemia in non-obese diabetes mice with severe combined immunodeficiency. Leukemia 30, 1749–1752 (2016). https://doi.org/10.1038/leu.2016.28

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