GITR-positive effector T cells are involved in AAF/PH mouse liver regeneration

Abstract

Abstract: Objective To observe the ratio variation of effector T lymphocytes during liver regeneration in 2-acetylaminofluorene/partial hepatectomy (AAF/PH) mouse. Methods After daily intragastric administration of AAF for 5 days, C57BL/6J mice were performed 1/3 hepatectomy followed by daily administration of AAF for 7 days or 14 days. Immune fluorescence staining and western blot were used to detect the activation of hepatic progenitor cells. Collagenase digestion and Percoll-density centrifugation were used to isolate liver non-parenchymal cells, and multi-color immune staining and flow cytometry were used to analyze the percentage of effector T lymphocytes and their glucocorticoid-induced TNF receptor (GITR)-positive ratio. Results On the 7th post-operative day, there was no significant difference with regard to liver weght between the AAF/PH and control groups. Although few inflammatory cells and no significant liver fibrosis were observed in the liver tissue of the AAF/PH group, the liver tissue showed significant inflammatory cell infiltration and extracellular matrix deposition at the portal area on the 14th post-operative day. After partial hepatectomy, the number of Sox9+ hepatic progenitor cells increased time-dependently, and the expression level of Sox9 also enhanced in the liver tissue. Flow cytometry analysis showed that the ratio of CD8⁺ T lymphocytes to CD3⁺ T lymphocytes increased after partial hepatectomy, while the ratio of CD8⁺GITR⁺ T cells increased at 7 days post-operation, when compared to the control group, but reduced to the level of the control group at 14 days post-operation. Although the ratio of CD4⁺ T lymphocytes to CD3⁺ T lymphocytes did not change significantly, the ratio of CD4⁺GITR⁺ T lymphocytes reduced significantly at 14 days post-operation compared to the control group.Conclusion AAF/PH activates hepatic progenitor cells in mouse liver regeneration model, and effector T cells are involved in mouse liver regeneration.

Key words: 2-acetylaminofluorene and partial hepatectomy, Hepatic progenitor cells, Glucocorticoid-induced TNF receptor

LI Li, HE Yu, LIU Kai, WANG Ping. GITR-positive effector T cells are involved in AAF/PH mouse liver regeneration[J]. Chinese Hepatolgy, 2023, 28(1): 112-116.

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