title: Dynamics of Circulating γδ T Cell Activity in an Immunocompetent Mouse Model of High-Grade Glioma.
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.
authors.affiliation: 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.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Beck
authors.affiliation: Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: Hyunggoon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Integrated Department of Immunology, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: O'Brien
authors.affiliation: Department of Pathology, University of California Irvine/Veterans Affairs Medical Center/Long Beach, Long Beach, California, 80206, United States of America.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jadus
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.affiliation: UAB Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine; Birmingham, Alabama, 35294, United States of America.
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Cloud
authors.affiliation: Department of Pathology, University of California Irvine/Veterans Affairs Medical Center/Long Beach, Long Beach, California, 80206, United States of America.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hoa
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Langford
authors.affiliation: Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lopez
authors.affiliation: Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: Lualhati E
authors.initials: LE
authors.lastname: Harkins
authors.affiliation: Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35294, United States of America.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lamb
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005910:Glioma / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4