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Regulatory T cells phenotype in different clinical forms of Chagas' disease.

de Araújo FF, Vitelli-Avelar DM, Teixeira-Carvalho A, Antas PR, Assis Silva Gomes J, Sathler-Avelar R, Otávio Costa Rocha M, Elói-Santos SM, Pinho RT, Correa-Oliveira R, Martins-Filho OA - PLoS Negl Trop Dis (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Brasil.

ABSTRACT
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.

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Related in: MedlinePlus

Analysis of Foxp3+ CD25High CD4+ regulatory T cells in the peripheral blood from chagasic patients.Representative dot plots illustrate that the increased levels of regulatory T cells observed in T. cruzi antigens-stimulated cultures from IND tend to be higher than that observed in CARD, and also reflect an increased level of Foxp3+ CD25+ cells in the IND group (bottom graphs). Quadrant statistics were used for data analysis, and the results are expressed as the percentage of positive cells within the CD25+ CD4+ selected lymphocytes. Reproduced and adapted from [20].
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pntd-0000992-g003: Analysis of Foxp3+ CD25High CD4+ regulatory T cells in the peripheral blood from chagasic patients.Representative dot plots illustrate that the increased levels of regulatory T cells observed in T. cruzi antigens-stimulated cultures from IND tend to be higher than that observed in CARD, and also reflect an increased level of Foxp3+ CD25+ cells in the IND group (bottom graphs). Quadrant statistics were used for data analysis, and the results are expressed as the percentage of positive cells within the CD25+ CD4+ selected lymphocytes. Reproduced and adapted from [20].

Mentions: In addition to the above shown cell surface markers, we evaluated the expression of Foxp3 by these cells. This marker has been shown to play a key role in Treg cell function and still represents a highly specific marker for these cells [50]–[54]. Previously published studies have consistently reported that Foxp3 is predominantly expressed by both human and murine CD25High CD4+ Treg cells. In agreement with previous data, increased levels of Foxp3+ CD25+ cells were also observed in the IND group after in vitro stimulation with T. cruzi antigens (Figure 3) [20], emphasizing once again the role of Treg cells in the control of Chagas' disease morbidity.


Regulatory T cells phenotype in different clinical forms of Chagas' disease.

de Araújo FF, Vitelli-Avelar DM, Teixeira-Carvalho A, Antas PR, Assis Silva Gomes J, Sathler-Avelar R, Otávio Costa Rocha M, Elói-Santos SM, Pinho RT, Correa-Oliveira R, Martins-Filho OA - PLoS Negl Trop Dis (2011)

Analysis of Foxp3+ CD25High CD4+ regulatory T cells in the peripheral blood from chagasic patients.Representative dot plots illustrate that the increased levels of regulatory T cells observed in T. cruzi antigens-stimulated cultures from IND tend to be higher than that observed in CARD, and also reflect an increased level of Foxp3+ CD25+ cells in the IND group (bottom graphs). Quadrant statistics were used for data analysis, and the results are expressed as the percentage of positive cells within the CD25+ CD4+ selected lymphocytes. Reproduced and adapted from [20].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104959&req=5

pntd-0000992-g003: Analysis of Foxp3+ CD25High CD4+ regulatory T cells in the peripheral blood from chagasic patients.Representative dot plots illustrate that the increased levels of regulatory T cells observed in T. cruzi antigens-stimulated cultures from IND tend to be higher than that observed in CARD, and also reflect an increased level of Foxp3+ CD25+ cells in the IND group (bottom graphs). Quadrant statistics were used for data analysis, and the results are expressed as the percentage of positive cells within the CD25+ CD4+ selected lymphocytes. Reproduced and adapted from [20].
Mentions: In addition to the above shown cell surface markers, we evaluated the expression of Foxp3 by these cells. This marker has been shown to play a key role in Treg cell function and still represents a highly specific marker for these cells [50]–[54]. Previously published studies have consistently reported that Foxp3 is predominantly expressed by both human and murine CD25High CD4+ Treg cells. In agreement with previous data, increased levels of Foxp3+ CD25+ cells were also observed in the IND group after in vitro stimulation with T. cruzi antigens (Figure 3) [20], emphasizing once again the role of Treg cells in the control of Chagas' disease morbidity.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Brasil.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus