Laboratory Investigation

Graefe's Archive for Clinical and Experimental Ophthalmology

, Volume 245, Issue 10, pp 1549-1557

First online:

CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber-associated immune deviation

  • Xuefei ZhuAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Peizeng YangAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University Email author 
  • , Hongyan ZhouAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Bing LiAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Xiangkun HuangAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Qianli MengAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Li WangAffiliated withState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University
  • , Aize KijlstraAffiliated withAnimal Sciences Group van Wageningen UR Divisie VeehouderijDepartment Ophthalmology, Eye Research Institute Maastricht, University of Maastricht

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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+CD25T 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.

Conclusion

Splenic CD4+CD25+Foxp3+T cells expressing CTLA4 and LAG3 play an important role in the induction of ACAID.

Keywords

Regulatory T cells Immune regulation Foxp3 ACAID