title: Characterization of the gammadelta T cell response to acute leukemia.
abstract: BACKGROUND
  Previous work from our center has suggested a correlation between increased donor-derived Vdelta1+ gammadelta T cells and long-term relapse-free survival following bone marrow transplantation for leukemia. Questions remain, however, as to whether this observation can be explained by a gammadelta T cell-based immune response against primary leukemia.
  
  
  METHODS
  We examined gammadelta T cell receptor (TCR) phenotype, cell proliferation, and cytolytic activity following culture with irradiated primary leukemia blasts from a haploidentical first-degree relative. Subsequently, we also studied the gammadelta TCR phenotype and complimentarity determining region 3 (CDR3) cDNA sequences from 17 newly diagnosed leukemia patients.
  
  
  RESULTS
  In 17/28 (61%) of in vitro cultures, gammadelta T cells proliferated in culture with primary blasts. Vdelta1+ T cells were proportionally increased in all cultures and were the predominant cell population in 6/17. In the 7 cultures where cytotoxicity could be assessed, 6 (86%) showed some degree of cytotoxicity to the primary leukemia. Vdelta1+ T cells were also the predominant gammadelta T cell subtype in pre-treatment leukemia patients principally due to loss of Vdelta2+ T cells rather than expansion of Vdelta1+ cells. The Vdelta1 CDR3-region cDNA sequence from these patients revealed exclusive use of the Jdelta1 constant region and sequence conservation in 4/11 patients.
  
  
  CONCLUSIONS
  gammadelta T cells exhibit an in vitro response to primary leukemia blasts that is manifested by proliferation, an increased proportion of Vdelta1+ T cells, and cytotoxicity to the primary leukemia blasts. The Vdelta1+ T cell population is also predominant in newly diagnosed leukemia patients likely due to a loss of circulating Vdelta2+ T cells. A small proportion of newly diagnosed patients showed Vdelta1 CDR3 region similarity. These findings suggest a role for gammadelta T cells in the immune response to leukemia.
authors.affiliation: Department of Pediatrics, University of South Carolina School of Medicine, Columbia, SC, 29203, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Meeh
authors.forename: Michelle
authors.initials: M
authors.lastname: King
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Stephanie
authors.initials: S
authors.lastname: Muga
authors.forename: Philip
authors.initials: P
authors.lastname: Buckhalts
authors.forename: Ronnie
authors.initials: R
authors.lastname: Neuberg
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lamb
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D016692:Receptors, Antigen, T-Cell, gamma-delta