Involvement of Foxp3-expressing CD4+ CD25+ regulatory T cells in the development of tolerance induced by transforming growth factor-beta2-treated antigen-presenting cells.
A growing body of evidence has shown that professional antigen-presenting cells (APC) treated with transforming growth factor-beta (TGF-beta) can induce a systemic antigen (Ag)-specific tolerance, similar to anterior chamber-associated immune deviation (ACAID). However, the exact mechanism for immune tolerance induced by TGF-beta-treated APC has not been elucidated. In this study, we showed that intravenous injection of ovalbumin (OVA)-pulsed APC treated with TGF-beta(2) induced a peripheral tolerance as evidenced by an impaired delayed-type hypersensitivity (DTH) response. CD4(+) T cells from mice receiving an intravenous injection of TGF-beta(2)-treated APC pulsed with OVA could adoptively transfer a specific tolerance to naïve mice. An increased frequency of FoxP3-expressing CD4(+) CD25(+) T cells was observed in mice with tolerance. CD4(+ )CD25(+) T cells from TGF-beta(2)-treated APC-injected mice produced a large amount of TGF-beta(1) and exhibited an in vitro antigen-specific suppressive activity. CD4(+) CD25(+) T cells from TGF-beta(2)-treated APC-injected mice were able to inhibit the antigen-specific DTH response significantly when adoptively transferred to naïve mice. These results indicate that FoxP3-expressing CD4(+) CD25(+) T cells might be actively involved in the development of tolerance induced by TGF-beta(2)-treated APC.
Zhang
Haining
H
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University, Zhongshan Ophthalmic Center, Guangzhou, China.
Yang
Peizeng
P
Zhou
Hongyan
H
Meng
Qianli
Q
Huang
Xiangkun
X
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053781:Transforming Growth Factor beta2 / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; C509042:Tgfb2 protein, mouse; D053781:Transforming Growth Factor beta2