Cancer Immunology, Immunotherapy

, Volume 57, Issue 12, pp 1807–1816

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

  • Abdeljabar El Andaloussi
  • Yu Han
  • Maciej S. Lesniak
Original Article

DOI: 10.1007/s00262-008-0508-3

Cite this article as:
Andaloussi, A.E., Han, Y. & Lesniak, M.S. Cancer Immunol Immunother (2008) 57: 1807. doi:10.1007/s00262-008-0508-3

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.

Keywords

Glioma Thymus Apoptosis Heme oxygenase-1 (HO-1) Notch Regulatory T-cell (CD4+CD25+Foxp3+

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Abdeljabar El Andaloussi
    • 1
    • 2
  • Yu Han
    • 1
  • Maciej S. Lesniak
    • 1
  1. 1.The Brain Tumor CenterThe University of ChicagoChicagoUSA
  2. 2.Division of Neurosurgery and Neuro-oncology, Faculty of Medicine and Health ScienceThe University of SherbrookeSherbrookeCanada