CD25(High) CD4+ regulatory T cells (Treg cells) have been described as key 
players in immune regulation, preventing infection-induced immune pathology and 
limiting collateral tissue damage caused by vigorous anti-parasite immune 
response. In this review, we summarize data obtained by the investigation of 
Treg cells in different clinical forms of Chagas' disease. Ex vivo 
immunophenotyping of whole blood, as well as after stimulation with Trypanosoma 
cruzi antigens, demonstrated that individuals in the indeterminate (IND) 
clinical form of the disease have a higher frequency of Treg cells, suggesting 
that an expansion of those cells could be beneficial, possibly by limiting 
strong cytotoxic activity and tissue damage. Additional analysis demonstrated an 
activated status of Treg cells based on low expression of CD62L and high 
expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. 
cruzi antigenic stimulation. Moreover, there was an increase in the frequency of 
the population of Foxp3+ CD25(High)CD4+ cells that was also IL-10+ in the IND 
group, whereas in the cardiac (CARD) group, there was an increase in the 
percentage of Foxp3+ CD25(High) CD4+ cells that expressed CTLA-4. These data 
suggest that IL-10 produced by Treg cells is effective in controlling disease 
development in IND patients. However, in CARD patients, the same regulatory 
mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient 
to control the progression of the disease. These data suggest that Treg cells 
may play an important role in controlling the immune response in Chagas' disease 
and the balance between regulatory and effector T cells may be important for the 
progression and development of the disease. Additional detailed analysis of the 
mechanisms on how these cells are activated and exert their function will 
certainly give insights for the rational design of procedure to achieve the 
appropriate balance between protection and pathology during parasite infections.