Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Department of Pathology and Laboratories, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Am J Trop Med Hyg. 2019 Feb;100(2):377-385. doi: 10.4269/ajtmh.18-0517.
Type 2 reaction (T2R) or (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8/TNF effector memory T cells (T) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8 IFN-γ-producing cells in T2R, and a reduced expression of and . Finally, a significant and positive correlation between bacteriological index (BI) of T2R patients and CD4/TNF and CD4/IFN-γ T cells was observed. Thus, negative correlation between BI and the frequency of CD4/IL-10 T cells was noted. These results suggest that CD8/TNF T are primarily responsible for the transient alteration in the immune response to in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.
2 型反应(T2R)或急性结节性红斑(ENL),是一种突然发作的急性炎症,主要影响瘤型麻风病(LL)患者,其特征是细胞免疫反应减弱。这可能表明 T2R 的发作与 T 淋巴细胞,尤其是记忆亚群的频率和功能活性的改变密切相关。本研究对有或无 T2R 的 LL 患者的 T 细胞血液亚群进行了体外和体外特征分析。此外,通过流式细胞术分析这些细胞产生 IFN-γ、TNF 和 IL-10 的频率来评估这些亚群的活性。此外,通过定量实时聚合酶链反应分析转录因子的表达,用于 T 细胞的分化。我们的结果显示,T2R 患者中 CD8/TNF 效应记忆 T 细胞(T)的频率增加。此外,T2R 中 CD4 和 CD8 IFN-γ产生细胞的频率降低, 和 的表达降低。最后,观察到 T2R 患者的细菌学指数(BI)与 CD4/TNF 和 CD4/IFN-γ T 细胞之间存在显著正相关。因此,BI 与 CD4/IL-10 T 细胞的频率之间存在负相关。这些结果表明,CD8/TNF T 细胞主要负责 ENL 患者对麻风分枝杆菌的免疫反应的短暂改变。因此,我们的研究加深了对发病机制的理解,并可能为麻风病提出新的治疗方法。