KLRG1-expressing CD8+T cells are exhausted and polyfunctional in patients with chronic hepatitis B

作者全名：Wang, Li; Liao, Fangli; Yang, Liping; Jiang, Linshan; Duan, Liang; Wang, Bo; Mu, Di; Chen, Juan; Huang, Ying; Hu, Qin; Chen, Weixian

作者地址：[Wang, Li; Liao, Fangli; Yang, Liping; Jiang, Linshan; Duan, Liang; Wang, Bo; Mu, Di; Hu, Qin; Chen, Weixian] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing, Peoples R China; [Chen, Juan] Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated, Chinese Minist Educ, Chongqing, Peoples R China; [Huang, Ying] Chongqing Med Univ, Affiliated Hosp 2, Dept Infect Dis, Chongqing, Peoples R China

通信作者：Hu, Q; Chen, WX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing, Peoples R China.

来源：PLOS ONE

ESI学科分类：Multidisciplinary

WOS号：WOS:001229236500039

JCR分区：Q1

影响因子：2.9

年份：2024

卷号：19

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

基金机构：National Natural Science Foundation of China [81672080, 81873971]

基金资助正文：WXC received National Natural Science Foundation of China (81672080, 81873971).