Improved effector function of leukemia-specific T-lymphocyte clones trained with AML-derived dendritic cells

Recently it was shown that myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DC_leu), regaining the stimulatory capacity of professional DCs while presenting the leukemic antigen repertoire. But so far, the induced antileukemic T-cell responses have varied in specificity and efficacy, or have even mediated opposite effects. In an attempt to further characterize the DC/ DC_leu induced T-cell response pattern, immunoscope spectratyping, a novel and powerful tool to detect T-cell receptor (TCR) rearrangements was used in combination with functional flow cytometry and non-radioactive fluorolysis assays. Human leucocyte antigen (HLA) matched donor T-cells were repeatedly stimulated, either with leukemic blasts (French-American-British, FAB M4eo) or the corresponding blast-derived DCs. Functional comparison revealed no significant difference in their T-cell stimulatory capacity, while the DC/DC_leu fraction favored T-cells with a higher lytic activity, comprising a higher proportion of T-memory CD45R0⁺ cells. Stimulation with blasts and DC/DC_leu induced a similar TCR restriction pattern, while stimulation with DC/DC_leu favored the CD4 T-cell subset and seemed to cause a higher grade of restriction. In conclusion, a combined strategy using spectratyping with functional tests might not only provide useful information about the specificity and efficacy of the induced T-cell response, but also pave the way to gain effective T-cell clones for therapeutic use.