Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease

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

Further evidence of spontaneous cure in human Chagas disease

An acute case of Chagas disease was studied in 1944, with clinical and laboratory follow-up until 2007, in Bambuí, Minas Gerais, Brazil. A five-year-old girl living in a rural hut that was highly infested with Triatoma infestans presented a febrile clinical condition compatible with the acute form of trypanosomiasis. She presented a positive thick blood smear, but never again showed serological and/or parasitological evidence of Trypanosoma cruzi infection, on several occasions. This patient never received any specific treatment and, to this day, she remains completely asymptomatic, with normal findings from clinical, electrocardiographic, X-ray and echocardiographic examinations

High frequencies of DN αβ T-cells are associated with TB severity.

<p>Representative contour plots showing the gate strategy used for the analysis of CD4 (middle left), CD8 (middle center), DN (middle right) αβ-T cells and the expression of CD69 (upper panels) and HLA-DR (lower panels) on DN αβ-T cells (A). Percentages of CD4⁺ (left panels), CD8⁺ (middle panels) and DN (right panels) αβ T-cells in healthy donors (HD, open symbols), TB (total TB, black symbols), nsTB (non-severe TB, light gray symbols) and sTB patients (severe TB, dark gray) were measured before treatment (B). The percentage of CD69 (C) and HLA-DR (D) expression within CD4⁺ (left panels), CD8⁺ (middle panels) and DN (right panels) αβ T-cells in HD, TB, nsTB and sTB patients were analyzed ex vivo. The boxes represent the means.</p

Higher frequencies of IFN-γ producing DN αβ T-cells are found in nsTB patients.

<p>Representative contour plots showing the proportions of IFN-γ producing CD4 (left panel), CD8 (middle panel) and DN (right panel) αβ-T cells (A). The percentages of IFN-γ (B), TNF-α (C) and IL-10 (D) expression within CD4⁺ (left panels), CD8⁺ (middle panels) and DN (right panels) αβ T-cells in healthy donors (HD, open symbols), TB (total TB, black symbols), nsTB (non-severe TB, light gray symbols) and sTB patients (severe TB, dark gray) were measured before treatment. PBMCs were stimulated with (MTB-Ag) for 48 hours. The boxes represent the means.</p

Advanced TB patients display decreased proportions of DN γδ T-cells.

<p>Representative contour plots showing the gate strategy used for the analysis of CD4 (middle left), CD8 (middle center), DN (middle right) γδ-T cells and the expression of CD69 (upper panels) and HLA-DR (lower panels) on DN γδ -T cells (A). Percentages of CD4⁺ (left panels), CD8⁺ (middle panels) and DN (right panels) γδ T-cells in healthy donors (HD, open symbols), TB (total TB, black symbols), nsTB (non-severe TB, light gray symbols) and sTB patients (severe TB, dark gray) were measured before treatment (B). The percentage of CD69 (C) and HLA-DR (D) expression within CD4⁺ (left panels), CD8⁺ (middle panels) and DN (right panels) γδ T-cells in HD, TB, nsTB and sTB patients were analyzed ex vivo. The boxes represent the means.</p