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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Autores principales: Grzywnowicz, Maciej, Zaleska, Joanna, Mertens, Daniel, Tomczak, Waldemar, Wlasiuk, Paulina, Kosior, Kamila, Piechnik, Agnieszka, Bojarska-Junak, Agnieszka, Dmoszynska, Anna, Giannopoulos, Krzysztof
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331976/
https://www.ncbi.nlm.nih.gov/pubmed/22532845
http://dx.doi.org/10.1371/journal.pone.0035178
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author Grzywnowicz, Maciej
Zaleska, Joanna
Mertens, Daniel
Tomczak, Waldemar
Wlasiuk, Paulina
Kosior, Kamila
Piechnik, Agnieszka
Bojarska-Junak, Agnieszka
Dmoszynska, Anna
Giannopoulos, Krzysztof
author_facet Grzywnowicz, Maciej
Zaleska, Joanna
Mertens, Daniel
Tomczak, Waldemar
Wlasiuk, Paulina
Kosior, Kamila
Piechnik, Agnieszka
Bojarska-Junak, Agnieszka
Dmoszynska, Anna
Giannopoulos, Krzysztof
author_sort Grzywnowicz, Maciej
collection PubMed
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.
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spelling pubmed-33319762012-04-24 Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic Leukemia Grzywnowicz, Maciej Zaleska, Joanna Mertens, Daniel Tomczak, Waldemar Wlasiuk, Paulina Kosior, Kamila Piechnik, Agnieszka Bojarska-Junak, Agnieszka Dmoszynska, Anna Giannopoulos, Krzysztof PLoS One Research Article 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. Public Library of Science 2012-04-19 /pmc/articles/PMC3331976/ /pubmed/22532845 http://dx.doi.org/10.1371/journal.pone.0035178 Text en Grzywnowicz 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grzywnowicz, Maciej
Zaleska, Joanna
Mertens, Daniel
Tomczak, Waldemar
Wlasiuk, Paulina
Kosior, Kamila
Piechnik, Agnieszka
Bojarska-Junak, Agnieszka
Dmoszynska, Anna
Giannopoulos, Krzysztof
Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic Leukemia
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331976/
https://www.ncbi.nlm.nih.gov/pubmed/22532845
http://dx.doi.org/10.1371/journal.pone.0035178
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