title: Impairment of CD4+CD25+ regulatory T cells in C4-deficient mice.
abstract: OBJECTIVE
  To investigate the association between deficiencies of early components in the classical complement pathway and the development of SLE.
  
  
  METHODS
  Forty inbred C57BL/6J mice and 40 knockout C4 complement gene (C4KO) mice, which included 10 mice in each age group (2, 4, 6, and 8 months) were used. The enumeration of CD4+CD25+ Tregs frequencies in bone marrow, spleen and peripheral blood from both normal and C4KO groups were performed by flow cytometry. The expression levels of Foxp3 and TGF-beta in the same tested tissues were measured using real time PCR. The antinuclear antibodies (ANA) were semi-quantitatively measured using ELISA.
  
  
  RESULTS
  We report decreased frequencies of CD4+CD25+ Tregs and reduced expression levels of Foxp3 and TGF-beta, which efficiently program the development and function of Tregs, in lymphoid tissues and peripheral blood of C4KO mice. In this study, C4KO mice have higher titers of ANA than those of normal mice. Higher frequencies of mice positive for ANA are also found in older mice.
  
  
  CONCLUSIONS
  The deficiency of the C4 gene induces the decreased numbers of Tregs that further increase the production of ANA resulting in the development of an autoimmune disorder. The outcomes of our study help us to understand the association between the deficiency of C4 in the classical complement pathway and development of autoimmune disorder via the role of Tregs.
authors: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors: Pornsawan
authors: P
authors: Leaungwutiwong
authors: Wannaporn
authors: W
authors: Ittiprasert
authors: Kulnasan
authors: K
authors: Saikhun
authors: Pirut
authors: P
authors: Tong-Ngam
authors: Siriwat
authors: S
authors: Akapirat
authors: Siriporn
authors: S
authors: Chattanadee
authors: Yindee
authors: Y
authors: Kitiyanant
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D003181:Complement C4 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D003181:Complement C4; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta