IL‐10 distinguishes a unique population of activated, effector‐like CD8+ T cells in murine acute liver inflammation. Issue 4 (29th December 2016)

• Record Type: Journal Article
• Authors: Rood, Julia E.; Canna, Scott W.; Weaver, Lehn K.; Tobias, John W.; Behrens, Edward M.
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 4(2017)
• Page Start: 1037
• Page End: 1044
• Publication Date: 2016-12-29
• Subjects: cytokine -- hemophagocytic syndrome -- hepatitis; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0916-221RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Systemic inflammation induces innate activation of effector‐like CD8 + T cells to infiltrate the liver and produce IL‐10. Abstract : Immune‐mediated liver injury is a central feature of hyperinflammatory diseases, such as hemophagocytic syndromes, yet the immunologic mechanisms underlying those processes are incompletely understood. In this study, we used the toll‐like receptor 9 (TLR9)–mediated model of a hemophagocytic syndrome known as macrophage activation syndrome (MAS) to dissect the predominant immune cell populations infiltrating the liver during inflammation. We identified CD8 + T cells that unexpectedly produce interleukin‐10 (IL‐10) in addition to interferon‐γ (IFN‐γ) as a major hepatic population induced by TLR9 stimulation. Despite their ability to produce this anti‐inflammatory cytokine, IL‐10 + hepatic CD8 + T cells in TLR9–MAS mice did not resemble CD8 + T suppressor cells. Instead, the induction of these cells occurred independently of antigen stimulation and was partially dependent on IFN‐γ. IL‐10 + hepatic CD8 + T cells demonstrated an activated phenotype and high turnover rate, consistent with an effector‐like identity. Transcriptional analysis of this population confirmed a gene signature of effector CD8 + T cells yet suggested responsiveness to liver injury–associated growth factors. Together, these findings suggest that IL‐10 + CD8 + T cells induced by systemic inflammation to infiltrate the liver have initiated an inflammatory, rather than regulatory, program and may thus have a pathogenic role in severe, acute hepatitis.