title: CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis.
abstract: BACKGROUND
  Previous studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice.
  
  
  METHODS
  Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-gamma (IFN-gamma) concentration was measured by ELISA.
  
  
  RESULTS
  hFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group [(23.4 +/- 4.3)% vs (6.6 +/- 2.5)%, P < 0.01]. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice [(1.0 +/- 0.5) vs (2.1 +/- 0.7), P < 0.001]. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-gamma concentration were significantly decreased in the CMV-hFasL transgenic mice.
  
  
  CONCLUSIONS
  FasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.
authors.affiliation: Center for Preventing and Treating Osteoporosis, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China. ZZL2002@madmail.com.cn
authors.forename: Zhen-lin
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.forename: Lu-yang
authors.initials: LY
authors.lastname: Yu
authors.forename: Li-he
authors.initials: LH
authors.lastname: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016516:CD4-CD8 Ratio; D003587:Cytomegalovirus / Q000235:genetics; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000517:prevention & control*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D007371:Interferon-gamma