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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Published in:PloS one 2012-04, Vol.7 (4), p.e35178-e35178
Main Authors: Grzywnowicz, Maciej, Zaleska, Joanna, Mertens, Daniel, Tomczak, Waldemar, Wlasiuk, Paulina, Kosior, Kamila, Piechnik, Agnieszka, Bojarska-Junak, Agnieszka, Dmoszynska, Anna, Giannopoulos, Krzysztof
Format: Article
Language:English
Subjects:
Aberration
Adult
Aged
Aged, 80 and over
Antigens
Apoptosis
B cells
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B7-H1 Antigen - genetics
B7-H1 Antigen - metabolism
Biology
Bone marrow
Cancer
CD38 antigen
CD40 Antigens - pharmacology
CD40L protein
Cell surface
Chronic lymphocytic leukemia
Female
Flow cytometry
Gene expression
Humans
Immunoglobulins
Immunological tolerance
Infections
Interleukin 4
Interleukin-4 - pharmacology
Internal medicine
Kinases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Ligands
Lymphatic leukemia
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Male
Medical prognosis
Medical research
Medicine
Middle Aged
Pathogenesis
Patients
PD-1 protein
PD-L1 protein
Phosphatase
Programmed Cell Death 1 Receptor - genetics
Programmed Cell Death 1 Receptor - metabolism
RNA
Signal transduction
Splicing
T cells
Viral infections
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cited_by cdi_FETCH-LOGICAL-c758t-9624abad324fede1bec9ec48409478168bf32b1c4ad88eff7d85aa85c62986a63
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container_end_page e35178
container_issue 4
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container_title PloS one
container_volume 7
creator Grzywnowicz, Maciej
Zaleska, Joanna
Mertens, Daniel
Tomczak, Waldemar
Wlasiuk, Paulina
Kosior, Kamila
Piechnik, Agnieszka
Bojarska-Junak, Agnieszka
Dmoszynska, Anna
Giannopoulos, Krzysztof
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
doi_str_mv 10.1371/journal.pone.0035178
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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grzywnowicz, Maciej</au><au>Zaleska, Joanna</au><au>Mertens, Daniel</au><au>Tomczak, Waldemar</au><au>Wlasiuk, Paulina</au><au>Kosior, Kamila</au><au>Piechnik, Agnieszka</au><au>Bojarska-Junak, Agnieszka</au><au>Dmoszynska, Anna</au><au>Giannopoulos, Krzysztof</au><au>Lapteva, Natalia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-04-19</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e35178</spage><epage>e35178</epage><pages>e35178-e35178</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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&lt;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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22532845</pmid><doi>10.1371/journal.pone.0035178</doi><tpages>e35178</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2012-04, Vol.7 (4), p.e35178-e35178
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1324573720
source PubMed Central (Open Access); Publicly Available Content Database (Proquest) (PQ_SDU_P3)
subjects Aberration
Adult
Aged
Aged, 80 and over
Antigens
Apoptosis
B cells
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B7-H1 Antigen - genetics
B7-H1 Antigen - metabolism
Biology
Bone marrow
Cancer
CD38 antigen
CD40 Antigens - pharmacology
CD40L protein
Cell surface
Chronic lymphocytic leukemia
Female
Flow cytometry
Gene expression
Humans
Immunoglobulins
Immunological tolerance
Infections
Interleukin 4
Interleukin-4 - pharmacology
Internal medicine
Kinases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Ligands
Lymphatic leukemia
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Male
Medical prognosis
Medical research
Medicine
Middle Aged
Pathogenesis
Patients
PD-1 protein
PD-L1 protein
Phosphatase
Programmed Cell Death 1 Receptor - genetics
Programmed Cell Death 1 Receptor - metabolism
RNA
Signal transduction
Splicing
T cells
Viral infections
title Programmed death-1 and its ligand are novel immunotolerant molecules expressed on leukemic B cells in chronic lymphocytic leukemia
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