Date: 31 May 2007

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

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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.

This study is supported by the Fund for the National Natural Science Foundation (30400487), Research Group Fund of Guangdong Province Natural Science (2005-04) and Innovation Research Groups of China (30321004).