Characterization of the gammadelta T cell response to acute leukemia.
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.
Meeh
Paul F
PF
Department of Pediatrics, University of South Carolina School of Medicine, Columbia, SC, 29203, USA.
King
Michelle
M
O'Brien
Rebecca L
RL
Muga
Stephanie
S
Buckhalts
Philip
P
Neuberg
Ronnie
R
Lamb
Lawrence S
LS
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*
D022801:Complementarity Determining Regions; D016692:Receptors, Antigen, T-Cell, gamma-delta