Characterization of the gammadelta T cell response to acute leukemia

Cancer Immunol Immunother. 2006 Sep;55(9):1072-80. doi: 10.1007/s00262-005-0094-6. Epub 2005 Nov 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Proliferation
  • Cells, Cultured
  • Complementarity Determining Regions / genetics
  • Cytotoxicity Tests, Immunologic
  • Female
  • Humans
  • Immunophenotyping*
  • Leukemia, Myeloid, Acute / immunology*
  • Lymphocyte Culture Test, Mixed
  • Male
  • Molecular Sequence Data
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Sequence Analysis, DNA
  • Survival Rate
  • T-Lymphocytes / immunology*


  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, gamma-delta