Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumorimmunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previouslyreported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity andupregulated Th1 responses in vivo. However, the underlying molecular mechanisms are not well understood. Here weshow that Treg function was significantly downregulated in mice that received immunization of attenuated activatedautologous 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 abilitycompared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high levelof anti-CD25 antibody (about 30ng/ml, p<0.01 vs controls). Consistent with a role of anti-CD25 response in the down-regulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Tregpopulation and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explainedby the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Ourresults demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggestthat dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of themechanism underlying the boosted anti-tumor immunity. Regulatory T cells (Tregs play important roles in immune system homeostasis, and may also be involved in tumorimmunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously carried the immunization with attenuated activated autologous T cells leads to enhanced anti However, the underlying molecular mechanisms are not well understood. Here weshow 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 extracted diminished immunosuppression ability to prepare from those from naive mice. Further analysis showed that the serum of immunized mice containing 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 down -regulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Tregpopulation 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 Con A activated autologous T cells used for immunization. Ourresults 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 suggestthat dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of themechanism underlying the boosted anti-tumor immunity.