Characterization of the gamma delta T cell response to acute leukemia

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2006-09, Vol.55 (9), p.1072-1080
• Main Authors: Meeh, P F, King, M, O'Brien, R L, Muga, S, Buckhalts, P, Neuberg, R, Lamb, LS Jr
• Format: Article
• Language: English
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-005-0094-6

Previous work from our center has suggested a correlation between increased donor-derived V delta 1 + gamma delta 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 gamma delta T cell-based immune response against primary leukemia. We examined gamma delta 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 gamma delta TCR phenotype and complimentarity determining region 3 (CDR3) cDNA sequences from 17 newly diagnosed leukemia patients. In 17/28 (61%) of in vitro cultures, gamma delta T cells proliferated in culture with primary blasts. V delta 1 + 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. V delta 1+ T cells were also the predominant gamma delta T cell subtype in pre-treatment leukemia patients principally due to loss of V delta 2+ T cells rather than expansion of V delta 1+ cells. The V delta 1 CDR3-region cDNA sequence from these patients revealed exclusive use of the J delta 1 constant region and sequence conservation in 4/11 patients. gamma delta T cells exhibit an in vitro response to primary leukemia blasts that is manifested by proliferation, an increased proportion of V delta 1+ T cells, and cytotoxicity to the primary leukemia blasts. The V delta 1+ T cell population is also predominant in newly diagnosed leukemia patients likely due to a loss of circulating V delta 2+ T cells. A small proportion of newly diagnosed patients showed V delta 1 CDR3 region similarity. These findings suggest a role for gamma delta T cells in the immune response to leukemia.