Abstract
CD25High 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+ CD25HighCD4+ 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+ CD25High 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.
Highlights
A substantial number of studies have been published on the analysis of the human immune response against the infection by the protozoa Trypanosoma cruzi
In an attempt to better characterize these cells in Chagas’ disease, we investigated whether CD25High CD4+ Treg in the peripheral blood of chagasic patients are IL-10 producers [20]
The available data do not cover all the gaps and did not address several questions regarding the mechanisms underlying the recruitment, activation, and function of regulatory T cells in development of tissue damage in Chagas’ disease patients, they give important insights to clearly emphasize that Treg cells are relevant to modulate the immune response in chronic human T. cruzi infection (Box 3)
Summary
A substantial number of studies have been published on the analysis of the human immune response against the infection by the protozoa Trypanosoma cruzi Those studies have evaluated the putative role of various cell populations, their subsets and cytokines, and their correlation with the regulation of the immune response during T. cruzi infection [1,2,3,4,5,6,7,8,9,10,11,12,13]. New data on the regulatory mechanisms that control diseases continue to accumulate, there is still significant need for further analysis of the various cell populations in T. cruzi infection that will allow testing of new hypotheses to elucidate the mechanisms that lead to the development of the different clinical forms of the disease as well as the mechanisms of protection. It is important to mention that the papers cited in this article were selected based on some criteria such as stringency of the papers in relation to the subjects discussed, high quality of papers, and papers indexed in the PubMed database (Box 1)
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