title: Inhibition of allogenic T-cell cytotoxicity by hepatic stellate cell via CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in vitro.
abstract: BACKGROUND
  The liver is considered to be an immune-privileged organ. Several types of liver cells have been implicated in the induction of immunologic tolerance. Hepatic stellate cells (HSCs) seem to participate in hepatic fibrosis and to display immunological properties.
  
  
  RESULTS
  In this study, HSCs isolated from C3H mice were highly positive for GFAP (98.4%) and α-SMA (95.4%). After stimulation by interferon-γ (IFN-γ), HSCs were more active in morphology with enhanced expression of H2-K(K), I-A(K), CD80, and CD54, similar to mature myelogenic dendritic cells (MDCs). Through allogeneic stimulation, C3H HSCs induced proliferation of both CD8(+) and CD4(+) T cells in B6 mice. However, the T cells activated by allogeneic HSCs produced less INF-γ, interleukin (IL)-4, IL-10, and IL-17, but large amount of transforming growth factor-β. These T cells expressed immunoregulatory rather than effector functions. Naïve T cells stimulated by allogeneic HSCs expressed Foxp3 compared with MDCs (8.67% vs 2.14%, P < .05). CD8(+) T cells activated by HSCs lost their allogeneic cytotoxicity, and CD4(+) T cells activated in this fashion suppressed the allogeneic cytotoxicity of CD8(+) T cells activated by MDCs.
  
  
  CONCLUSIONS
  HSCs seem to act as liver-resident antigen-presenting cells instructing the generation of Foxp3(+) regulatory T cells, a property suggestion of induction of immunologic tolerance.
authors.affiliation: Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung, Taiwan.
authors.forename: T-J
authors.initials: TJ
authors.lastname: Wu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.forename: T-H
authors.initials: TH
authors.lastname: Wu
authors.forename: C-F
authors.initials: CF
authors.lastname: Lee
authors.forename: K-M
authors.initials: KM
authors.lastname: Chan
authors.forename: W-C
authors.initials: WC
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D048430:Cell Shape; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma