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Erschienen in:

01.12.2022 | Original Article

Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function

verfasst von: Ying Gao, Lan Li, Xingxing Hu, Weihua Zhang, Yu Li

Erschienen in: Archivum Immunologiae et Therapiae Experimentalis | Ausgabe 1/2022

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Abstract

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.
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Metadaten
Titel
Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8+ T Cell Function
verfasst von
Ying Gao
Lan Li
Xingxing Hu
Weihua Zhang
Yu Li
Publikationsdatum
01.12.2022
Verlag
Springer International Publishing
Erschienen in
Archivum Immunologiae et Therapiae Experimentalis / Ausgabe 1/2022
Print ISSN: 0004-069X
Elektronische ISSN: 1661-4917
DOI
https://doi.org/10.1007/s00005-022-00663-8