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...

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Bibliographic Details
Published in:PloS one 2018-01, Vol.13 (1), p.e0191482-e0191482
Main Authors: Koldehoff, Michael, Lindemann, Monika, Ross, Stefan R, Elmaagacli, Ahmet H
Format: Article
Language:English
Subjects:
Activation
Acute myeloid leukemia
Antigens
Apoptosis
Biology and Life Sciences
Biotechnology
Bone marrow
Cell culture
Cell growth
Cell Line, Tumor
Coculture Techniques
Consent
Cytokines
Cytomegalovirus
Dioxygenase
Experiments
Flow cytometry
Ganciclovir
Granzyme B
Health risks
Hematopoietic stem cells
Histocompatibility antigen HLA
Histocompatibility Antigens Class II - immunology
Hospitals
Humans
Immunoglobulins
Infections
Leukemia
Leukemia, Myeloid, Acute - immunology
Leukemia, Myeloid, Acute - therapy
Leukemia, Myeloid, Acute - virology
Leukocytes (mononuclear)
Lymphocytes
Lymphoma
Medicine and Health Sciences
Myeloid leukemia
Oligonucleotides
Perforin
Peripheral blood mononuclear cells
Promyeloid leukemia
Research and Analysis Methods
Risk management
Risk reduction
Secretion
Stem Cell Transplantation
Stem cells
Transplantation
Transplantation, Homologous
Transplants & implants
γ-Interferon
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0191482