Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li
{"title":"白细胞介素-35可能通过抑制CD8+ T细胞功能在传染性单核细胞增多症诱导的肝脏炎症中发挥保护作用","authors":"Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li","doi":"10.1007/s00005-022-00663-8","DOIUrl":null,"url":null,"abstract":"<div><p>Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8<sup>+</sup> T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8<sup>+</sup> T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8<sup>+</sup> T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8<sup>+</sup> T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8<sup>+</sup> T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8<sup>+</sup> T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8<sup>+</sup> T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8<sup>+</sup> T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8<sup>+</sup> T cell-induced liver inflammation in patients with IM.</p></div>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function\",\"authors\":\"Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li\",\"doi\":\"10.1007/s00005-022-00663-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8<sup>+</sup> T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8<sup>+</sup> T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8<sup>+</sup> T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8<sup>+</sup> T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8<sup>+</sup> T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8<sup>+</sup> T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8<sup>+</sup> T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8<sup>+</sup> T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8<sup>+</sup> T cell-induced liver inflammation in patients with IM.</p></div>\",\"PeriodicalId\":8389,\"journal\":{\"name\":\"Archivum Immunologiae et Therapiae Experimentalis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2022-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archivum Immunologiae et Therapiae Experimentalis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00005-022-00663-8\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archivum Immunologiae et Therapiae Experimentalis","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00005-022-00663-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function
Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8+ T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8+ T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8+ T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8+ T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8+ T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8+ T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8+ T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8+ T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8+ T cell-induced liver inflammation in patients with IM.
期刊介绍:
Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.