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

Friedhelm R. Schuster, Raymund Buhmann, Susanne Reuther, Bernd Hubner, Christine Grabrucker, Anja Liepert, Roland Reibke, Peter Lichtner, Ting Yang, Tanja Kroell, Hans Jochem Kolb, Arndt Borkhardt, Helga Schmetzer

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Recently it was shown that myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DCleu), 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/ DCleu 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/DCleu fraction favored T-cells with a higher lytic activity, comprising a higher proportion of T-memory CD45R0+ cells. Stimulation with blasts and DC/DCleu induced a similar TCR restriction pattern, while stimulation with DC/DCleu 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.

Original languageEnglish
Pages (from-to)275-286
Number of pages12
JournalCancer Genomics and Proteomics
Volume5
Issue number5
StatePublished - 2008
Externally publishedYes

Keywords

  • AML
  • DC
  • Immunotherapy
  • Spectratyping
  • Stem cell transplantation
  • T-cells

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