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Am J Trop Med Hyg ; 100(2): 377-385, 2019 02.
Article in English | MEDLINE | ID: mdl-30652669

ABSTRACT

Type 2 reaction (T2R) or erythema nodosum leprosum (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 (TEM) 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 STAT4 and TBX21. 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+ TEM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Erythema Nodosum/immunology , Leprosy, Lepromatous/immunology , Mycobacterium leprae/pathogenicity , Tumor Necrosis Factor-alpha/immunology , Adolescent , Adult , Aged , CD4-Positive T-Lymphocytes/microbiology , CD8-Positive T-Lymphocytes/microbiology , Case-Control Studies , Erythema Nodosum/genetics , Erythema Nodosum/pathology , Female , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-10/genetics , Interleukin-10/immunology , Leprosy, Lepromatous/genetics , Leprosy, Lepromatous/pathology , Male , Middle Aged , Mycobacterium leprae/growth & development , Mycobacterium leprae/immunology , Primary Cell Culture , STAT4 Transcription Factor/genetics , STAT4 Transcription Factor/immunology , Signal Transduction , T-Box Domain Proteins/genetics , T-Box Domain Proteins/immunology , Tumor Necrosis Factor-alpha/genetics
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