| First Author | Rood JE | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 101 |
| Issue | 4 | Pages | 1037-1044 |
| PubMed ID | 28034913 | Mgi Jnum | J:274533 |
| Mgi Id | MGI:6295301 | Doi | 10.1189/jlb.3A0916-221RR |
| Citation | Rood JE, et al. (2017) IL-10 distinguishes a unique population of activated, effector-like CD8(+) T cells in murine acute liver inflammation. J Leukoc Biol 101(4):1037-1044 |
| abstractText | 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-gamma (IFN-gamma) 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-gamma. 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. |
