[HTML][HTML] Dynamics of circulating γδ T cell activity in an immunocompetent mouse model of high-grade glioma

BH Beck, H Kim, R O'Brien, MR Jadus, GY Gillespie… - PLoS …, 2015 - journals.plos.org
BH Beck, H Kim, R O'Brien, MR Jadus, GY Gillespie, GA Cloud, NT Hoa, CP Langford…
PLoS One, 2015journals.plos.org
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 …
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.
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