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 (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.
Schuster
Friedhelm R
FR
Department of Pediatric Oncology, Hematology and Immunology, Heinrich Heine University Medical Center, Dusseldorf, Germany.
Buhmann
Raymund
R
Reuther
Susanne
S
Hubner
Bernd
B
Grabrucker
Christine
C
Liepert
Anja
A
Reibke
Roland
R
Lichtner
Peter
P
Yang
Ting
T
Kroell
Tanja
T
Kolb
Hans-Jochem
HJ
Borkhardt
Arndt
A
Schmetzer
Helga
H
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001752:Blast Crisis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta