title: CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation.
abstract: BACKGROUND
  Regulatory CD4(+)CD25(+) T cells have been proven to be essential for maintenance of peripheral tolerance and autoimmune diseases. ACAID is a model of immune privilege in the eye. Relatively little is known about the role and phenotype of these regulatory CD4(+)CD25(+) T cells in ACAID.
  
  
  METHODS
  Injection of OVA into the anterior chamber of BALB/C mice was performed to induce ACAID. The frequencies of splenic CD4(+)CD25(+) Tregs and the expression of CTLA-4 and LAG-3 on these cells were determined by flow cytometry. Magnetic cell sorting was used to isolate CD4(+)CD25(+) and CD4(+)CD25(-)T cells. The function of CD4(+)CD25(+) T cells was detected by in vitro immunosuppression assays and in vivo adoptive transfer.
  
  
  RESULTS
  ACAID was successfully induced following an i.c. injection of OVA. Frequencies of CD4(+)CD25(+) and Tregs were significantly increased in ACAID mice as compared to those in controls. The CD4(+)CD25(+) T cells stimulated with OVA in ACAID mice showed a stronger suppressive ability in vitro than those seen in non-ACAID mice. CD4(+)CD25(+) T cells from ACAID mice, but not from non-ACAID mice, were able to suppress DTH responses in an antigen-specific manner following adoptive transfer. The frequencies of CTLA-4 or LAG-3 on Tregs in ACAID mice were higher as compared with those in naive mice.
  
  
  CONCLUSIONS
  Splenic CD4(+)CD25(+)Foxp3(+)T cells expressing CTLA4 and LAG3 play an important role in the induction of ACAID.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou 510060, People's Republic of China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Zhu
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Xiangkun
authors.initials: X
authors.lastname: Huang
authors.forename: Qianli
authors.initials: Q
authors.lastname: Meng
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010047:Ovalbumin; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse