Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C

In chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4<sup>+</sup>CD8<sup>+</sup>) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells...

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Main Authors: Anna Maria Kochanowicz, Sylwia Osuch, Hanna Berak, Aleksandra Kumorek, Kamila Caraballo Cortés
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/10/1446
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author Anna Maria Kochanowicz
Sylwia Osuch
Hanna Berak
Aleksandra Kumorek
Kamila Caraballo Cortés
author_facet Anna Maria Kochanowicz
Sylwia Osuch
Hanna Berak
Aleksandra Kumorek
Kamila Caraballo Cortés
author_sort Anna Maria Kochanowicz
collection DOAJ
description In chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4<sup>+</sup>CD8<sup>+</sup>) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells, including HCV-specific cells, and assessed the effect of successful HCV treatment on inhibitory receptors expression. Blood samples from 97 CHC patients were collected before and six months post-treatment. PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) expression was assessed by flow cytometry. DP T-cells displayed significantly higher PD-1 expression, lower Tim-3 expression than CD8<sup>+</sup> SP T-cells and lower percentages of PD-1<sup>−</sup>Tim-3<sup>−</sup> cells than CD4<sup>+</sup> SP T-cells, both before and after treatment. PD-1<sup>+</sup>Tim-3<sup>+</sup> DP T-cells decreased following treatment. HCV-specific cells were more frequent among DP than SP T-cells, both before and after treatment. HCV-specific DP T-cells were characterized by lower PD-1 expression, higher PD-1 and Tim-3 co-expression, and lower percentages of PD-1<sup>−</sup>Tim-3<sup>−</sup> cells (both before and after treatment) and higher post-treatment Tim-3 than HCV-specific SP T-cells. Their percentages decreased following treatment, but the exhaustion phenotype remained unchanged. DP T-cells in CHC exhibit a distinct exhaustion phenotype from SP T-cells, and these changes mostly persist following successful treatment.
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spelling doaj.art-6f6ef1d40d2b4437b5eea93d0a1b443d2023-11-18T00:53:43ZengMDPI AGCells2073-44092023-05-011210144610.3390/cells12101446Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis CAnna Maria Kochanowicz0Sylwia Osuch1Hanna Berak2Aleksandra Kumorek3Kamila Caraballo Cortés4Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, PolandOutpatient Clinic, Warsaw Hospital for Infectious Diseases, 01-201 Warsaw, PolandDepartment of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, PolandIn chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4<sup>+</sup>CD8<sup>+</sup>) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells, including HCV-specific cells, and assessed the effect of successful HCV treatment on inhibitory receptors expression. Blood samples from 97 CHC patients were collected before and six months post-treatment. PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) expression was assessed by flow cytometry. DP T-cells displayed significantly higher PD-1 expression, lower Tim-3 expression than CD8<sup>+</sup> SP T-cells and lower percentages of PD-1<sup>−</sup>Tim-3<sup>−</sup> cells than CD4<sup>+</sup> SP T-cells, both before and after treatment. PD-1<sup>+</sup>Tim-3<sup>+</sup> DP T-cells decreased following treatment. HCV-specific cells were more frequent among DP than SP T-cells, both before and after treatment. HCV-specific DP T-cells were characterized by lower PD-1 expression, higher PD-1 and Tim-3 co-expression, and lower percentages of PD-1<sup>−</sup>Tim-3<sup>−</sup> cells (both before and after treatment) and higher post-treatment Tim-3 than HCV-specific SP T-cells. Their percentages decreased following treatment, but the exhaustion phenotype remained unchanged. DP T-cells in CHC exhibit a distinct exhaustion phenotype from SP T-cells, and these changes mostly persist following successful treatment.https://www.mdpi.com/2073-4409/12/10/1446CD4<sup>+</sup>CD8<sup>+</sup> double positive (DP) T-cellshepatitis C virusantiviral treatmentDAAT-cell exhaustionPD-1
spellingShingle Anna Maria Kochanowicz
Sylwia Osuch
Hanna Berak
Aleksandra Kumorek
Kamila Caraballo Cortés
Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
Cells
CD4<sup>+</sup>CD8<sup>+</sup> double positive (DP) T-cells
hepatitis C virus
antiviral treatment
DAA
T-cell exhaustion
PD-1
title Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
title_full Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
title_fullStr Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
title_full_unstemmed Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
title_short Double Positive CD4<sup>+</sup>CD8<sup>+</sup> (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C
title_sort double positive cd4 sup sup cd8 sup sup dp t cells display distinct exhaustion phenotype in chronic hepatitis c
topic CD4<sup>+</sup>CD8<sup>+</sup> double positive (DP) T-cells
hepatitis C virus
antiviral treatment
DAA
T-cell exhaustion
PD-1
url https://www.mdpi.com/2073-4409/12/10/1446
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