title: [Changes of regulatory T cells related to CCl₄-induced liver fibrosis in mice].
abstract: OBJECTIVE
  To investigate liver fibrosis-related changes of CD4⁺CD25⁺Foxp3+ regulatory T cells (Tregs) in peripheral blood and in liver-infiltrating lymphocytes (LILs) using a mouse model.
  
  
  METHODS
  C57BL/6 mice were randomly divided into a model group and a control group. The model group received intraperitoneal injection of carbon tetrachloride (CC1₄) to induce liver fibrosis, and the control group received an equal volume of physiological saline. Serum was collected for detection of alanine aminotransferase level. Histopathological changes in liver were assessed by microscopic observation of tissues stained by hematoxylineosin and Masson. Frequencies of peripheral and intrahepatic Tregs, NK1.1⁺ cells, CD4⁺ and CD8⁺ cells were analyzed by flow cytometry. Intrahepatic Foxp3+ cells were detected by immunofluorescence. Liver expression of IL-6, IL-10, TGFb and Foxp3 was measured by RT-PCR detection of mRNA .Inter-group differences were evaluated by t-test.
  
  
  RESULTS
  The model group showed a significantly higher frequency of intrahepatic CD25⁺Foxp3⁺/CD4⁺ Tregs (10.63% ± 1.50% vs. control group:1.80% ± 0.66%; P less than 0.01) but only slightly higher frequency of peripheral Tregs (6.00% ± 0.62% vs. 5.33% ± 2.86%). The model group also showed significantly higher levels of intrahepatic Foxp3+ cells and of Foxp3 mRNA (both P less than 0.05), but significantly lower frequencies of NK1.1 cells in LILs (9.53% ± 2.25% vs. 19.80% ± 5.97%; P less than 0.05) and in peripheral blood (0.38% ± 0.13% vs. 1.06% ± 0.63%; P less than 0.05). The CD4⁺ cell frequency and the CD4⁺/CD8⁺ ratio were lower in LILs and peripheral blood of the model group, but none differed significantly from the control group. The intrahepatic expression of TGFb mRNA was significantly higher in the model group (P less than 0.01).
  
  
  CONCLUSIONS
  In liver fibrosis, intrahepatic CD4⁺CD25⁺Foxp3+ Tregs are increased while NK1.1+ cells are decreased. Tregs may suppress NK1.1+ cells through a mechanism involving TGFb.
authors.affiliation: Clinical Laboratory Center, Beijing You'an hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Jinli
authors.initials: J
authors.lastname: Lou
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory