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

Cancer Genomics Proteomics. 2008 Sep-Oct;5(5):275-86.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Blast Crisis*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Rearrangement
  • Humans
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Lymphocyte Activation
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • Receptors, Antigen, T-Cell, alpha-beta