Imbalanced IL10/TGF-β production by regulatory T-lymphocytes in patients with HTLV-1-associated myelopathy/ tropical spastic paraparesis

Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs)...

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Published in:	BMC infectious diseases Vol. 24; no. 1; pp. 652 - 10
Main Authors:	Gois, Luana Leandro, Ribeiro-Soares, Bárbara, Regis-Silva, Carlos Gustavo, Zanette, Dalila L, Lisboa, Raphaella, Nascimento, Regina Santos, Coutinho Junior, Raimundo, Galvão-Castro, Bernardo, Grassi, Maria Fernanda Rios
Format:	Journal Article
Language:	English
Published:	England BioMed Central 28-06-2024 BMC
Subjects:	Adult Aged Asymptomatic Carrier State - immunology Carrier State - virology CD4 antigen CD8 antigen Cell activation Cell cycle Central nervous system diseases Cytokines Dermatitis Female Flow cytometry Gene expression Genomes Health care Hereditary spastic paraplegia HTLV-1 HTLV-associated myelopathy HTLV-I Infections - immunology HTLV-I Infections - virology Human T-lymphotropic virus 1 - immunology Humans IL10 Immune response Infections Inflammation Inflammatory response Interleukin 10 Interleukin-10 - genetics Interleukin-10 - immunology Leukemia Leukocytes (mononuclear) Lymphocytes Lymphocytes T Male Middle Aged Paraparesis, Tropical Spastic - immunology Paraparesis, Tropical Spastic - virology Peripheral blood mononuclear cells Polymerase chain reaction Population studies Proteins Regulatory T lymphocytes Reverse transcription Software Spinal cord T-Lymphocytes, Regulatory - immunology TGF-β Transforming Growth Factor beta - metabolism Transforming growth factor-b Tropical spastic paraparesis Viral infections Viral Load Brazil United States > US IL10 TGF-β HTLV-1 Regulatory T lymphocytes HTLV-associated myelopathy
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Summary:	Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-β. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines. Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells. Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group. A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2334 1471-2334
DOI:	10.1186/s12879-024-09494-8