Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Antileukemic T-cell responses can be predicted by the composition of specific regulatory T-cell subpopulations.
J. Immunother. 36, 223-237 (2013)
Regulatory T cells (T-reg) are important regulators of immune responses. In acute myeloid leukemia (AML) patients before/after immunotherapy (stem cell transplantation or donor lymphocyte infusion), their suppressive role can contribute to suppress severe graft-versus-host reactions, but also to impair antileukemic reactions. As leukemia-derived dendritic cells (DCleu) are known to improve the antileukemic functionality of T cells, we evaluated the composition and development of distinct T-reg subtypes in AML patients (n = 12) compared with healthy probands (n = 5) under unstimulated conditions and during stimulation with DCleu-containing DC (DC) or blast-containing mononuclear cells (MNC) in 0- to 7-day mixed lymphocyte cultures by flow cytometry. T-cell subgroups in AML patients were correlated with antileukemic functionality before and after DC or MNC stimulation by functional fluorolysis assays. (1) AML patients' T cells presented with significantly higher frequencies of T-reg subgroups in unstimulated T cells compared with healthy probands. (2) After 7 days of DC or MNC stimulation, all T-reg subtypes generally increased; significantly higher frequencies of Treg subtypes were still found in AML patients. (3) Antileukemic cytotoxicity was achieved in 36% of T cells after MNC compared with 64% after DC stimulation. Antileukemic activity after DC but not after MNC stimulation correlated with significantly lower frequencies of T-reg subtypes (CD8(+) T-reg/T-eff/em reg). Furthermore, cut-off values for T-reg subpopulations could be defined, allowing a prediction of antileukemic response. We demonstrate a crucial role of special T-reg subtypes in the mediation of antileukemic functionality. High CD8(+) T-reg, T-eff/em reg, and CD39(+) T cells correlated clearly with a reduced antileukemic activity of T cells. DC stimulation of T cells contributes to overcome impaired antileukemic T-cell reactivity. Refined analyses in the context of clinical responses to immunotherapies and graft versus host reactions are required.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Aml ; Regulatory T Cells ; Dendritic Cells ; Immune Escape; Versus-host-disease ; Acute Myeloid-leukemia ; Continuous Antigen Stimulation ; Bone-marrow-transplantation ; Dendritic Cells ; Tgf-beta ; Peripheral-blood ; 4-1bb Ligand ; Ex-vivo ; Expression
ISSN (print) / ISBN
1524-9557
e-ISSN
1537-4513
Zeitschrift
Journal of Immunotherapy
Quellenangaben
Band: 36,
Heft: 4,
Seiten: 223-237
Verlag
Lippincott Williams & Wilkins
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Hematopoetic Cell Transplants (IMI-KHZ)