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
Departamento de Morfologia, Laboratório de Biologia das Interações Celulares, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Instituto René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Brazil.
Front Cardiovasc Med. 2022 May 19;9:750876. doi: 10.3389/fcvm.2022.750876. eCollection 2022.
Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of the chronic phase of Chagas disease caused by infection. It was described as the most fibrosing cardiomyopathies, affecting approximately 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, 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. To characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4 (Th1, Th2, Th17, and Treg) and CD8 T lymphocyte subsets, we used blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with antigens from non-infected (NI), IND, and CARD individuals. We demonstrated a higher frequency of CD8 CD25 T lymphocytes and CD8 Treg cells after anti-CD80 antibody blockade only in the CARD group. In contrast, a lower frequency of CD4 Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. A higher frequency of CD4 Treg CD28 lymphocytes, as well as an association between CD4 Treg lymphocytes and CD28 expression on CD4 Treg cells in the CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade, was observed. We proposed that Treg cells from IND patients could be activated 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 cell activation CD28 receptor. For the first time, our data highlight the role of CD80 in modulation of Treg lymphocytes activation in patients with CARD, highlighting a key molecule in the development of Chagas cardiomyopathy.
恰加斯心肌病是由感染引起的恰加斯病慢性期的有症状心脏临床类型（CARD）。它被描述为纤维化程度最高的心肌病之一，在慢性期约30%的患者会受影响。还描述了其他不太常见的有症状临床类型。然而，大多数进展到慢性期的患者会发展为不确定临床类型（IND），可能终生无症状，或出现一些心脏损害。已经对恰加斯病临床类型病因中的一些机制进行了研究。为了表征共刺激分子CD8 和CD86在不同CD4（Th1、Th2、Th17和Treg）和CD8 T淋巴细胞亚群激活中的作用，我们在含有来自未感染（NI）、IND和CARD个体抗原的培养物中，对外周血单个核细胞（PBMC）的CD80和CD86受体使用了阻断抗体。我们发现，仅在CARD组中，抗CD80抗体阻断后CD8 CD25 T淋巴细胞和CD8 Treg细胞的频率更高。相反，仅在IND患者中发现抗CD86抗体阻断后CD4 Treg淋巴细胞的频率较低。在CARD组中观察到CD4 Treg CD28淋巴细胞频率更高，以及CD4 Treg淋巴细胞与CD4 Treg细胞上CD28表达之间的关联，但IND患者中未观察到，且同样仅在抗CD80抗体阻断后出现。我们提出，IND患者的Treg细胞可能通过CD86 - CTLA - 4相互作用被激活，从而仅在恰加斯病无症状患者中调节免疫反应，而CD80可能参与T CD8淋巴细胞的增殖控制，以及调节性细胞通过CD28受体的激活。我们的数据首次强调了CD80在CARD患者Treg淋巴细胞激活调节中的作用，突出了其在恰加斯心肌病发展中的关键分子地位。
