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

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.

• Authors: Abdeljabar El Andaloussi, Yu Han, Maciej S Lesniak
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 57 Issue 12 Pg. 1807-16 (Dec 2008) ISSN: 0340-7004 [Print] Germany
• PMID: 18392618 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Intercellular Signaling Peptides and Proteins
• Jag1 protein, mouse
• Jagged-1 Protein
• Membrane Proteins
• Receptor, Notch1
• Serrate-Jagged Proteins
• Heme Oxygenase-1

Topics

• Animals
• Apoptosis (immunology)
• Brain Neoplasms (immunology, metabolism, pathology)
• Calcium-Binding Proteins (biosynthesis)
• Cell Differentiation (immunology)
• Disease Progression
• Flow Cytometry
• Glioma (immunology, metabolism, pathology)
• Heme Oxygenase-1 (biosynthesis)
• Homeostasis
• Intercellular Signaling Peptides and Proteins (biosynthesis)
• Jagged-1 Protein
• Male
• Membrane Proteins (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Receptor, Notch1 (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Serrate-Jagged Proteins
• T-Lymphocyte Subsets (cytology, immunology, metabolism)
• T-Lymphocytes (cytology, immunology, pathology)
• Thymus Gland (immunology, pathology)