PD1 and PDL1 molecules control suppressor activity of regulatory T cells in chronic Chagas cardiomyopathy patients

• Published in: Human immunology 2019-07, Vol.80 (7), p.517-522
• Main Authors: Damasio, Marcos P.S., Rocha, Manoel O.C., Sousa, Giovane R., Ferreira, Karine S., Fares-Gusmão, Rafaelle C.G., Medeiros, Nayara I., Araujo, Fernanda F., Chaves, Ana T., Dutra, Walderez O., Correa-Oliveira, Rodrigo, Gomes, Juliana A.S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, Protozoan - immunology; Apoptosis - immunology; Apoptotic mechanisms; Apyrase - metabolism; B7-H1 Antigen - metabolism; Cardiomyopathy, Dilated - blood; CD4 Antigens - metabolism; Chagas Cardiomyopathy - immunology; Chagas disease; Female; Forkhead Transcription Factors - metabolism; Humans; Interleukin-2 Receptor alpha Subunit - metabolism; Male; Middle Aged; Programmed Cell Death 1 Receptor - metabolism; Regulatory T cells; Serologic Tests; T-Lymphocytes, Regulatory - immunology; Trypanosoma cruzi - immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2019.03.009

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the fourth most important tropical disease, which affects approximately 7 million people worldwide. The mechanisms involved in the development of this disease are not completely well understood. An important protective role of regulatory T cells (Treg) in Chagas disease has been observed; however, the specific mechanisms remain unclear. We evaluated apoptosis as a possible mechanism mediated by Treg cells (CD4+CD25HighFOXP3+) to orchestrate the immune response in chronic Chagas disease. Patients with Chagas disease were grouped as the indeterminate (IND; asymptomatic patients with Chagas disease; n = 10) and dilated cardiomyopathy (CARD; n = 10). Healthy T. cruzi-negative individuals (NI; n = 10) were included as a control group. In order to evaluate the apoptotic cell profile, the expression of PD1, PD1L, CD39, CD95, CD95L molecules were investigated. We also evaluated the proportion of CD14+ cells expressing caspase 3. The IND group presented a substantially higher expression of CD39 by Treg cells as compared to the CARD group. On the other hand, the CARD group showed higher expression of PD-1 by Treg cells than both NI and IND groups. Significant positive correlations were observed between Treg CD95L+ cells and CD14 cells expressing caspase 3 as well as between Treg CD39 cells and CD14+ Caspase3+ cells in the IND group. Our data indicate that the expressions of different molecules that induce apoptosis are associated with suppressive mechanisms mediated by Treg cells and suggest a possible role for PD1 and PDL1 molecules in the morbidity of chronic Chagas disease.