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Progression of intracranial glioma disrupts thymic homeostasis and induces T-cell apoptosis in vivo

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Abstract

The thymus is the site where all T-cell precursors develop, mature, and subsequently leave as mature T-cells. Since the mechanisms that mediate and regulate thymic apoptosis are not fully understood, we utilized a syngenic GL261 murine glioma model to further elucidate the fate of T-cells in tumor bearing C57BL/6 mice. First, we found a dramatic reduction in the size of the thymus accompanied by a decrease in thymic cellularity in response to glioma growth in the brains of affected mice. There was a marked reduction of double positive subset and an increase in the frequency of CD4+ and CD8+ single positive T-cell subsets. Analysis of double negative thymocytes showed an increase in the accumulation of CD44+ cells. In contrast, there was a marked loss of CD44 and CD122 expression in CD4+ and CD8+ subsets. The growth of intracranial tumors was also associated with decreased levels of HO-1, a mediator of anti-apoptotic function, and increased levels of Notch-1 and its ligand, Jagged-1. To determine whether thymic atrophy could be due to the effect of Notch and its ligand expression by glioma in vivo, we performed a bone marrow transplant experiment. Our results suggest that Notch-1 and its ligand Jagged-1 can induce apoptosis of thymocytes, thereby influencing thymic development, immune system homeostasis, and function of the immune cells in a model of experimental glioma.

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Acknowledgments

We gratefully acknowledge the editorial assistance of Cleo Rolle, PhD. This study was supported by the Elsa U. Pardee Foundation as well as the Brain Research Foundation.

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Authors and Affiliations

  1. The Brain Tumor Center, The University of Chicago, 5841 S. Maryland Ave MC 3026, Chicago, IL, 60637, USA

    Abdeljabar El Andaloussi, Yu Han & Maciej S. Lesniak

  2. Division of Neurosurgery and Neuro-oncology, Faculty of Medicine and Health Science, The University of Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada

    Abdeljabar El Andaloussi

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  1. Abdeljabar El Andaloussi
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Correspondence to Maciej S. Lesniak.

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Andaloussi, A.E., Han, Y. & Lesniak, M.S. Progression of intracranial glioma disrupts thymic homeostasis and induces T-cell apoptosis in vivo. Cancer Immunol Immunother 57, 1807–1816 (2008). https://doi.org/10.1007/s00262-008-0508-3

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  • DOI: https://doi.org/10.1007/s00262-008-0508-3

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