AUTHOR=Pinto Bruna F. , Medeiros Nayara I. , Teixeira-Carvalho Andrea , Fiuza Jacqueline A. , Eloi-Santos Silvana M. , Nunes Maria C. P. , Silva Silvana A. , Fontes-Cal Tereza C. M. , Belchior-Bezerra Mayara , Dutra Walderez O. , Correa-Oliveira Rodrigo , Gomes Juliana A. S. 

TITLE=Modulation of Regulatory T Cells Activity by Distinct CD80 and CD86 Interactions With CD28/CTLA-4 in Chagas Cardiomyopathy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.750876

DOI=10.3389/fcvm.2022.750876

ISSN=2297-055X

ABSTRACT=Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of chronic phase of Chagas disease caused by Trypanosoma cruzi infection. It was described as the most fibrosing among cardiomyopathies, affecting about 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, the most patients who progress to the chronic form develop the indeterminate clinical form (IND), may remain asymptomatic for life or develop some cardiac damage. Some mechanisms involved in the etiology of the clinical forms of Chagas disease have been investigated. In order to characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4+ (Th1, Th2, Th17, Treg) and CD8+ T lymphocyte subsets, we use blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with T. cruzi antigens from non-infected (NI), IND and CARD individuals. We demonstrated higher frequency of CD8+ CD25+ T lymphocytes and CD8+ Treg cells after anti-CD80 antibody blockade only in CARD group. In contrast, lower frequency of CD4+ Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. Higher frequency of CD4+ Treg CD28+ lymphocytes, as well as an association between CD4+ Treg lymphocytes and CD28+ expression on CD4+ Treg cells in CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade was observed. We propose that Treg cells from IND patients could be activated via CD86-CTLA-4 interaction, leading to modulation of the immune response only in asymptomatic patients with Chagas disease, while CD80 may be involved in the proliferation control of T CD8+ lymphocytes, as also in the modulation of regulatory cells activation via CD28 receptor. Our data highlight for the first time the role of CD80 in modulation of Treg lymphocytes activation in CARD patients, pointing out a key molecule in the development of Chagas cardiomyopathy.