Cargando…

Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line

Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic hematopoietic stem cell transplantation (alloSCT) and is associated with an increased treatment-related mortality. Recent reports suggest a link between HCMV and a reduced risk of cancer progression in patients with acute leuke...

Descripción completa

Detalles Bibliográficos
Autores principales: Koldehoff, Michael, Lindemann, Monika, Ross, Stefan R., Elmaagacli, Ahmet H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788343/
https://www.ncbi.nlm.nih.gov/pubmed/29377903
http://dx.doi.org/10.1371/journal.pone.0191482
_version_ 1783296070264029184
author Koldehoff, Michael
Lindemann, Monika
Ross, Stefan R.
Elmaagacli, Ahmet H.
author_facet Koldehoff, Michael
Lindemann, Monika
Ross, Stefan R.
Elmaagacli, Ahmet H.
author_sort Koldehoff, Michael
collection PubMed
description Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic hematopoietic stem cell transplantation (alloSCT) and is associated with an increased treatment-related mortality. Recent reports suggest a link between HCMV and a reduced risk of cancer progression in patients with acute leukemia or lymphoma after alloSCT. Here we show that HCMV can inhibit the proliferation of the acute myeloid leukemia cell line Kasumi-1 and the promyeloid leukemia cell line NB4. HCMV induced a significant up-regulation of HLA-class-II-molecules, especially HLA-DR expression and an increase of apoptosis, granzyme B, perforin and IFN-γ secretion in Kasumi-1 cells cocultured with peripheral blood mononuclear cells (PBMCs). Indolamin-2,3-dioxygenase on the other hand led only to a significant dose-dependent effect on IFN-γ secretion without effects on proliferation. The addition of CpG-rich oligonucleotides and ganciclovir reversed those antiproliferative effects. We conclude that HCMV can enhance alloreactivity of PBMCs against Kasumi-1 and NB4 cells in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required.
format Online
Article
Text
id pubmed-5788343
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-57883432018-02-09 Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line Koldehoff, Michael Lindemann, Monika Ross, Stefan R. Elmaagacli, Ahmet H. PLoS One Research Article Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic hematopoietic stem cell transplantation (alloSCT) and is associated with an increased treatment-related mortality. Recent reports suggest a link between HCMV and a reduced risk of cancer progression in patients with acute leukemia or lymphoma after alloSCT. Here we show that HCMV can inhibit the proliferation of the acute myeloid leukemia cell line Kasumi-1 and the promyeloid leukemia cell line NB4. HCMV induced a significant up-regulation of HLA-class-II-molecules, especially HLA-DR expression and an increase of apoptosis, granzyme B, perforin and IFN-γ secretion in Kasumi-1 cells cocultured with peripheral blood mononuclear cells (PBMCs). Indolamin-2,3-dioxygenase on the other hand led only to a significant dose-dependent effect on IFN-γ secretion without effects on proliferation. The addition of CpG-rich oligonucleotides and ganciclovir reversed those antiproliferative effects. We conclude that HCMV can enhance alloreactivity of PBMCs against Kasumi-1 and NB4 cells in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required. Public Library of Science 2018-01-29 /pmc/articles/PMC5788343/ /pubmed/29377903 http://dx.doi.org/10.1371/journal.pone.0191482 Text en © 2018 Koldehoff et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Koldehoff, Michael
Lindemann, Monika
Ross, Stefan R.
Elmaagacli, Ahmet H.
Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title_full Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title_fullStr Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title_full_unstemmed Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title_short Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute myeloid leukemia cell line
title_sort cytomegalovirus induces hla-class-ii-restricted alloreactivity in an acute myeloid leukemia cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788343/
https://www.ncbi.nlm.nih.gov/pubmed/29377903
http://dx.doi.org/10.1371/journal.pone.0191482
work_keys_str_mv AT koldehoffmichael cytomegalovirusinduceshlaclassiirestrictedalloreactivityinanacutemyeloidleukemiacellline
AT lindemannmonika cytomegalovirusinduceshlaclassiirestrictedalloreactivityinanacutemyeloidleukemiacellline
AT rossstefanr cytomegalovirusinduceshlaclassiirestrictedalloreactivityinanacutemyeloidleukemiacellline
AT elmaagacliahmeth cytomegalovirusinduceshlaclassiirestrictedalloreactivityinanacutemyeloidleukemiacellline