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Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells.
Cell Res 2007; 17(7):627-37CR

Abstract

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 naïve 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 naïve 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.

Authors+Show Affiliations

Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17563757

Citation

Cao, Qi, et al. "Downregulation of CD4+CD25+ Regulatory T Cells May Underlie Enhanced Th1 Immunity Caused By Immunization With Activated Autologous T Cells." Cell Research, vol. 17, no. 7, 2007, pp. 627-37.
Cao Q, Wang L, Du F, et al. Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells. Cell Res. 2007;17(7):627-37.
Cao, Q., Wang, L., Du, F., Sheng, H., Zhang, Y., Wu, J., ... Li, N. (2007). Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells. Cell Research, 17(7), pp. 627-37.
Cao Q, et al. Downregulation of CD4+CD25+ Regulatory T Cells May Underlie Enhanced Th1 Immunity Caused By Immunization With Activated Autologous T Cells. Cell Res. 2007;17(7):627-37. PubMed PMID: 17563757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells. AU - Cao,Qi, AU - Wang,Li, AU - Du,Fang, AU - Sheng,Huiming, AU - Zhang,Yan, AU - Wu,Juanjuan, AU - Shen,Baihua, AU - Shen,Tianwei, AU - Zhang,Jingwu, AU - Li,Dangsheng, AU - Li,Ningli, PY - 2007/6/15/pubmed PY - 2007/10/4/medline PY - 2007/6/15/entrez SP - 627 EP - 37 JF - Cell research JO - Cell Res. VL - 17 IS - 7 N2 - 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 naïve 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 naïve 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. SN - 1748-7838 UR - https://www.unboundmedicine.com/medline/citation/17563757/Downregulation_of_CD4+CD25+_regulatory_T_cells_may_underlie_enhanced_Th1_immunity_caused_by_immunization_with_activated_autologous_T_cells_ L2 - http://dx.doi.org/10.1038/cr.2007.46 DB - PRIME DP - Unbound Medicine ER -