TY - JOUR
T1 - Improved effector function of leukemia-specific T-lymphocyte clones trained with AML-derived dendritic cells
AU - Schuster, Friedhelm R.
AU - Buhmann, Raymund
AU - Reuther, Susanne
AU - Hubner, Bernd
AU - Grabrucker, Christine
AU - Liepert, Anja
AU - Reibke, Roland
AU - Lichtner, Peter
AU - Yang, Ting
AU - Kroell, Tanja
AU - Kolb, Hans Jochem
AU - Borkhardt, Arndt
AU - Schmetzer, Helga
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - AML
KW - DC
KW - Immunotherapy
KW - Spectratyping
KW - Stem cell transplantation
KW - T-cells
UR - http://www.scopus.com/inward/record.url?scp=57249091723&partnerID=8YFLogxK
M3 - Article
C2 - 19129558
AN - SCOPUS:57249091723
SN - 1109-6535
VL - 5
SP - 275
EP - 286
JO - Cancer Genomics and Proteomics
JF - Cancer Genomics and Proteomics
IS - 5
ER -