Volume 17, No 7, Jul 2007
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 17 Issue 7, July 2007: 627-637
ORIGINAL ARTICLES
Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells
Qi Cao1,2,*, Li Wang1,2,*, Fang Du1,2, Huiming Sheng1,2, Yan Zhang1,2, Juanjuan Wu1,2, Baihua Shen1,2, Tianwei Shen1,2, Jingwu Zhang1,2, Dangsheng Li3 and Ningli Li1,2
1Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Shanghai Institute of Immunology, 280 South Chongqing Road, Shanghai 200025, China
3Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Correspondence: Ningli Li(ninglixiaoxue57@yahoo.com.cn)
Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Th1 responses
in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from na飗e mice. Further analysis showed that the serum of immunized mice contains a high level of anti-CD25 antibody (about 30 ng/ml,
p<0.01 vs controls). Consistent with a role of anti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to na飗e mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Th1 response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.
Cell Research (2007) 17:627-637. doi: 10.1038/cr.2007.46; published online 12 June 2007
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