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PLoS One. 2015 May 8;10(5):e0122387. doi: 10.1371/journal.pone.0122387. eCollection 2015.

Dynamics of Circulating γδ T Cell Activity in an Immunocompetent Mouse Model of High-Grade Glioma.

Author information

1
Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America; Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
2
Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
3
Integrated Department of Immunology, National Jewish Health, Denver, Colorado, United States of America.
4
Department of Pathology, University of California Irvine/Veterans Affairs Medical Center/Long Beach, Long Beach, California, 80206, United States of America.
5
Department of Neurosurgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
6
UAB Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine; Birmingham, Alabama, 35294, United States of America.

Abstract

Human γδ T cells are potent effectors against glioma cell lines in vitro and in human/mouse xenograft models of glioblastoma, however, this effect has not been investigated in an immunocompetent mouse model. In this report, we established GL261 intracranial gliomas in syngeneic WT C57BL/6 mice and measured circulating γδ T cell count, phenotype, Vγ/Vδ repertoire, tumor histopathology, NKG2D ligands expression, and T cell invasion at day 10-12 post-injection and at end stage. Circulating γδ T cells transiently increased and upregulated Annexin V expression at post-tumor day 10-12 followed by a dramatic decline in γδ T cell count at end stage. T cell receptor repertoire showed no changes in Vγ1, Vγ4, Vγ7 or Vδ1 subsets from controls at post-tumor day 10-12 or at end stage except for an end-stage increase in the Vδ4 population. Approximately 12% of γδ T cells produced IFN-γ. IL-17 and IL-4 producing γδ T cells were not detected. Tumor progression was the same in TCRδ-/- C57BL/6 mice as that observed in WT mice, suggesting that γδ T cells exerted neither a regulatory nor a sustainable cytotoxic effect on the tumor. WT mice that received an intracranial injection of γδ T cells 15m following tumor placement showed evidence of local tumor growth inhibition but this was insufficient to confer a survival advantage over untreated controls. Taken together, our findings suggest that an early nonspecific proliferation of γδ T cells followed by their depletion occurs in mice implanted with syngeneic GL261 gliomas. The mechanism by which γδ T cell expansion occurs remains a subject for further investigation of the mechanisms responsible for this immune response in the setting of high-grade glioma.

PMID:
25955158
PMCID:
PMC4425513
DOI:
10.1371/journal.pone.0122387
[Indexed for MEDLINE]
Free PMC Article

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