Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients
BackgroundPatients with chronic hepatitis B virus (HBV) infection are characterized by impaired immune response that fails to eliminate HBV. Immune checkpoint molecules (ICMs) control the amplitude of the activation and function of immune cells, which makes them the key regulators of immune response...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1489770/full |
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| author | Lucile Dumolard Marie-Noelle Hilleret Marie-Noelle Hilleret Charlotte Costentin Charlotte Costentin Marion Mercey-Ressejac Marion Mercey-Ressejac Nathalie Sturm Nathalie Sturm Theophile Gerster Thomas Decaens Thomas Decaens Evelyne Jouvin-Marche Patrice N. Marche Zuzana Macek Jilkova Zuzana Macek Jilkova |
| author_facet | Lucile Dumolard Marie-Noelle Hilleret Marie-Noelle Hilleret Charlotte Costentin Charlotte Costentin Marion Mercey-Ressejac Marion Mercey-Ressejac Nathalie Sturm Nathalie Sturm Theophile Gerster Thomas Decaens Thomas Decaens Evelyne Jouvin-Marche Patrice N. Marche Zuzana Macek Jilkova Zuzana Macek Jilkova |
| author_sort | Lucile Dumolard |
| collection | DOAJ |
| description | BackgroundPatients with chronic hepatitis B virus (HBV) infection are characterized by impaired immune response that fails to eliminate HBV. Immune checkpoint molecules (ICMs) control the amplitude of the activation and function of immune cells, which makes them the key regulators of immune response.MethodsWe performed a multiparametric flow cytometry analysis of ICMs and determined their expression on intrahepatic lymphocyte subsets in untreated and treated patients with HBV in comparison with non-pathological liver tissue.ResultsThe liver of untreated HBV patients exhibited a high accumulation of PD-1+CD8+ T cells, while the frequencies of 4-1BB+ T cells, 4-1BB+ natural killer (NK) cells, and TIM-3+CD8+ T cells were the highest in the chronic hepatitis phase. Our findings showed that the HBeAg status is linked to a distinct immune phenotype of intrahepatic CD8+ T cells and NK cells characterized by high expression of ICMs, particularly 4-1BB. Importantly, antiviral treatment partially restored the normal expression of ICMs. Finally, we described important differences in ICM expression between intrahepatic and circulating NK cells in HBV patients.ConclusionsOur study shows clear differences in the intrahepatic expression of ICMs on NK cells and T cells in chronic HBV patients depending on their clinical stage. |
| format | Article |
| id | doaj-art-a67f2883c05642a18189fcb8f48f9b75 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a67f2883c05642a18189fcb8f48f9b752025-01-15T05:10:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14897701489770Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patientsLucile Dumolard0Marie-Noelle Hilleret1Marie-Noelle Hilleret2Charlotte Costentin3Charlotte Costentin4Marion Mercey-Ressejac5Marion Mercey-Ressejac6Nathalie Sturm7Nathalie Sturm8Theophile Gerster9Thomas Decaens10Thomas Decaens11Evelyne Jouvin-Marche12Patrice N. Marche13Zuzana Macek Jilkova14Zuzana Macek Jilkova15Univ. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceService d’anatomie et de cytologie pathologiques, CHU Grenoble Alpes, Grenoble, FranceTranslational Research in Autoimmunity and Inflammation Group (TRAIG), Translational Innovation in Medicine and Complexity (TIMC), University Grenoble-Alpes, CNRS Unité mixte de recherche (UMR) 5525, La Tronche, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceUniv. Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, FranceService d’hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, La Tronche, FranceBackgroundPatients with chronic hepatitis B virus (HBV) infection are characterized by impaired immune response that fails to eliminate HBV. Immune checkpoint molecules (ICMs) control the amplitude of the activation and function of immune cells, which makes them the key regulators of immune response.MethodsWe performed a multiparametric flow cytometry analysis of ICMs and determined their expression on intrahepatic lymphocyte subsets in untreated and treated patients with HBV in comparison with non-pathological liver tissue.ResultsThe liver of untreated HBV patients exhibited a high accumulation of PD-1+CD8+ T cells, while the frequencies of 4-1BB+ T cells, 4-1BB+ natural killer (NK) cells, and TIM-3+CD8+ T cells were the highest in the chronic hepatitis phase. Our findings showed that the HBeAg status is linked to a distinct immune phenotype of intrahepatic CD8+ T cells and NK cells characterized by high expression of ICMs, particularly 4-1BB. Importantly, antiviral treatment partially restored the normal expression of ICMs. Finally, we described important differences in ICM expression between intrahepatic and circulating NK cells in HBV patients.ConclusionsOur study shows clear differences in the intrahepatic expression of ICMs on NK cells and T cells in chronic HBV patients depending on their clinical stage.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1489770/fullHBVPD-14-1BBimmune checkpoint moleculesliverT cells |
| spellingShingle | Lucile Dumolard Marie-Noelle Hilleret Marie-Noelle Hilleret Charlotte Costentin Charlotte Costentin Marion Mercey-Ressejac Marion Mercey-Ressejac Nathalie Sturm Nathalie Sturm Theophile Gerster Thomas Decaens Thomas Decaens Evelyne Jouvin-Marche Patrice N. Marche Zuzana Macek Jilkova Zuzana Macek Jilkova Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients Frontiers in Immunology HBV PD-1 4-1BB immune checkpoint molecules liver T cells |
| title | Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients |
| title_full | Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients |
| title_fullStr | Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients |
| title_full_unstemmed | Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients |
| title_short | Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients |
| title_sort | differences in the intrahepatic expression of immune checkpoint molecules on t cells and natural killer cells in chronic hbv patients |
| topic | HBV PD-1 4-1BB immune checkpoint molecules liver T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1489770/full |
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