Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia.
Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometri...
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2012-01-01
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doaj-c3adf016380e46eea0c976e5a853291e2021-03-04T00:51:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3517810.1371/journal.pone.0035178Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia.Maciej GrzywnowiczJoanna ZaleskaDaniel MertensWaldemar TomczakPaulina WlasiukKamila KosiorAgnieszka PiechnikAgnieszka Bojarska-JunakAnna DmoszynskaKrzysztof GiannopoulosProgrammed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22532845/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maciej Grzywnowicz Joanna Zaleska Daniel Mertens Waldemar Tomczak Paulina Wlasiuk Kamila Kosior Agnieszka Piechnik Agnieszka Bojarska-Junak Anna Dmoszynska Krzysztof Giannopoulos |
spellingShingle |
Maciej Grzywnowicz Joanna Zaleska Daniel Mertens Waldemar Tomczak Paulina Wlasiuk Kamila Kosior Agnieszka Piechnik Agnieszka Bojarska-Junak Anna Dmoszynska Krzysztof Giannopoulos Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. PLoS ONE |
author_facet |
Maciej Grzywnowicz Joanna Zaleska Daniel Mertens Waldemar Tomczak Paulina Wlasiuk Kamila Kosior Agnieszka Piechnik Agnieszka Bojarska-Junak Anna Dmoszynska Krzysztof Giannopoulos |
author_sort |
Maciej Grzywnowicz |
title |
Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. |
title_short |
Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. |
title_full |
Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. |
title_fullStr |
Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. |
title_full_unstemmed |
Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia. |
title_sort |
programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic b cells in chronic lymphocytic leukemia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22532845/?tool=EBI |
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