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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1489770

Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients

Provisionally accepted
Lucile Dumolard Lucile Dumolard 1Marie-Noelle Hilleret Marie-Noelle Hilleret 1,2Charlotte Costentin Charlotte Costentin 1,2Marion Mercey-Ressejac Marion Mercey-Ressejac 1,2Nathalie Sturm Nathalie Sturm 3Theophile Gerster Theophile Gerster 2Thomas Decaens Thomas Decaens 1,2Evelyne Jouvin-Marche Evelyne Jouvin-Marche 1Patrice N Marche Patrice N Marche 1Zuzana MACEK JILKOVA Zuzana MACEK JILKOVA 1,2*
  • 1 Univ. Grenoble Alpes, Institute for Advanced Biosciences, CNRS UMR5309, INSERM U1209, Grenoble, France, Grenoble, Rhône-Alpes, France
  • 2 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
  • 3 Service d’anatomo-pathologie, Pôle de Biologie, CHU Grenoble Alpes, 38700,, La Tronche, France

The final, formatted version of the article will be published soon.

    Patients with chronic hepatitis B virus (HBV) infection are characterised by impaired immune response that failed to eliminate HBV. Immune checkpoint molecules (ICM) control the amplitude of the activation and function of immune cells, that makes them the key regulators of the immune response.We performed a multiparametric flow cytometry analysis of ICM and determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with HBV in comparison with nonpathological liver tissue.Liver of untreated HBV patients exhibited high accumulation of PD-1 + CD8 + T cells while the frequencies of 4-1BB + T cells, 4-1BB + NK cells and TIM-3 + CD8 + T cells, were highest in 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 characterised by high expression of ICM, particularly 4-1BB. Importantly, antiviral treatment partially restored the normal expression of ICM. Finally, we described important differences in ICM expression between intrahepatic and circulating NK cells in HBV patients.Our study shows clear differences in the intrahepatic expression of ICM on NK cells and T cells in chronic HBV patients depending on their clinical stage.

    Keywords: HBV, PD-1, 4-1BB, immune checkpoint molecules, Liver, T cells, NK cells

    Received: 01 Sep 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Dumolard, Hilleret, Costentin, Mercey-Ressejac, Sturm, Gerster, Decaens, Jouvin-Marche, Marche and MACEK JILKOVA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zuzana MACEK JILKOVA, Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France

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