Análise fenotípica dos mecanismos de imunorregulação induzidos pelas células TREGSCD4+CD25HIGHFOXP3+ na Hanseníase

Abstract

Leprosy, caused by the non-culturable bacteria, Mycobacterium leprae (M. leprae), has several clinical manifestations, which are associated with the hosts immune responses. Dichotomy among the functions of T cells and antibodies is discussed based on current information on cytokines, subsets of T cells and regulatory T cells. Regulatory T cells CD4+CD25highFOXP3+ (TREGS) have been shown to be able to control the immune response by suppressing antigen-presenting cells and effector T cells. Some mechanisms induced by these cells have been proposed in leprosy infections. Nevertheless, the importance of immunoregulatory mechanisms of regulatory T cells still has not been completely established for this disease. The objective of the present study is to evaluate the expression of immunosuppression markers induced by regulatory T cells, present in the blood of patients with polar clinical forms of leprosy, household contacts and uninfected individuals. It is a cross-sectional analytical study with a quantitative approach. Individuals in the study were new cases of leprosy diagnosed at the Sanitary Dermatology Outpatient Service of Hospital Eduardo de Menezes, household contacts and uninfected individuals as control group. All patients were studied before treatment and were grouped according to Ridley and Jopling classification. Regulatory T cells have been quantified and immunophenotyping assays have been carried out in peripheral blood mononuclear cells with polar forms of leprosy, household contacts and controls. Quantification analyses of Regularoty T cells, immunophenotyping assays were performed by means of flow cytometry and of FlowJo software. Statistical tests such as ANOVA, Shapiro-Wilk normality test and Kruskal-Wallis, Mann-Whitney tests and Spearman correlation test were carried out in this study and analyzed using the SPSS software version 18.1 and the Cytoscape program, respectively. The study was approved by the Committee of Ethics in Research of Universidade Federal de Minas Gerais and the consent term was obtained from all participants. Thirteen new cases of leprosy, 14 household contacts and 15 controls took part in this study. Most patients were grouped in the LL (Lepromatous leprosy) polar clinical form (4 females and 4 males, average age = 52 years) or in household contacts with the clinical form (5 females and 5 males; mean age = 25 years). Regulatory T cells were more frequent in the LL polar clinical form. In the analysis of the Regulatory T cells induced immunnoregulation mechanisms, the suppression of effective T cells would be related to inhibiting mechanisms of cytokine (IL-10), to anergy induced by antigen-presenting cells (CTLA-4) and to the metabolic pathway interruption (CD39-CD73). Self-apoptosis of regulatory T cells, present in the polar clinical form, would be related to the control of an exacerbated immune response. Nevertheless, in the LL polar clinical form, the action of the apoptosis induction mechanism via CD95L and PD-1, associated with a higher frequency of regulatory T cells in this polar clinical form, would be related to apoptosis induction of effector cells, thus contributing to the viability of the bacillus and the persistence of the disease.