Determination of T Cell Responses in Thai Systemic Sclerosis Patients

Objectives. This study is aimed at determining the role of T cells by assessing the numbers of IFN-γ- and IL-2-secreting T cells following stimulation with peptides derived from DNA topoisomerase-I protein in Thai SSc patients. Methods. Fifty Thai SSc patients and 50 healthy controls (HC) joined thi...

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Main Authors: Oranit Likhit, Worawit Louthrenoo, Sa-nga Pattanakitsakul, Aroonroong Suttitheptumrong, Supot Hannongbua, Thanyada Rungrotmongkol, Hiroshi Noguchi, Fujio Takeuchi, Kobporn Boonnak
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/5072154
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author Oranit Likhit
Worawit Louthrenoo
Sa-nga Pattanakitsakul
Aroonroong Suttitheptumrong
Supot Hannongbua
Thanyada Rungrotmongkol
Hiroshi Noguchi
Fujio Takeuchi
Kobporn Boonnak
author_facet Oranit Likhit
Worawit Louthrenoo
Sa-nga Pattanakitsakul
Aroonroong Suttitheptumrong
Supot Hannongbua
Thanyada Rungrotmongkol
Hiroshi Noguchi
Fujio Takeuchi
Kobporn Boonnak
author_sort Oranit Likhit
collection DOAJ
description Objectives. This study is aimed at determining the role of T cells by assessing the numbers of IFN-γ- and IL-2-secreting T cells following stimulation with peptides derived from DNA topoisomerase-I protein in Thai SSc patients. Methods. Fifty Thai SSc patients and 50 healthy controls (HC) joined this study. IFN-γ and IL-2 levels upon stimulation of T cells with 6 peptides derived from DNA topoisomerase-I protein were determined. Anti-nuclear antibodies (ANA) and anti-Scl-70 antibodies were determined by using the ELISA method. Results. In SSc patients, we detected a significantly higher number of IFN-γ- and IL-2-secreting CD8+ T cells than IFN-γ- and IL-2-secreting CD4+ T cells after stimulation with pooled peptides derived from DNA topoisomerase-I protein. A similar percentage of CD4+IL-2+, CD4+IFN-γ+, and CD8+IL-2+ were detected following stimulation with DNA topoisomerase-I protein -in SSc patients with anti-Scl-70 antibody (SSc/anti-Scl-70+) and those without. In contrast, the amount of CD8+IFN-γ+ cells was significantly higher in SSc/anti-Scl-70+ than those without. Stimulation with individual peptides showed that CSLRVEHINLHPELD (sPep3; 15 amino acids; position 505-519 of DNA topoisomerase-I protein) was the optimal epitope that induced T cells secreting the highest levels of IFN-γ and IL-2. A higher percentage of IFN-γ+CD4+ T cells was detected in SSc/anti-Scl-70+ than those without the following stimulation with peptides 2 (amino acid position 475-486 [RAVALYFIDKLA] of protein DNA topoisomerase). Conclusion. The results from this study emphasize the critical role of DNA topoisomerase-I peptides on the activation of T cells in SSc patients. The findings provide a better understanding of SSc’s immunopathogenesis and may lead to the development of diagnostic tools and specific treatments for SSc in the future.
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spelling doaj-art-2c126ef70e474883a50bb8b3bbf4518b2025-08-20T02:24:07ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/5072154Determination of T Cell Responses in Thai Systemic Sclerosis PatientsOranit Likhit0Worawit Louthrenoo1Sa-nga Pattanakitsakul2Aroonroong Suttitheptumrong3Supot Hannongbua4Thanyada Rungrotmongkol5Hiroshi Noguchi6Fujio Takeuchi7Kobporn Boonnak8Department of Microbiology and ImmunologyDivision of RheumatologyDivision of Molecular MedicineDivision of Molecular MedicineThe Center of Excellence in Computational ChemistryBiocatalyst and Environmental Biotechnology Research UnitSchool of PharmacySchool of Pharmaceutical ScienceDepartment of ImmunologyObjectives. This study is aimed at determining the role of T cells by assessing the numbers of IFN-γ- and IL-2-secreting T cells following stimulation with peptides derived from DNA topoisomerase-I protein in Thai SSc patients. Methods. Fifty Thai SSc patients and 50 healthy controls (HC) joined this study. IFN-γ and IL-2 levels upon stimulation of T cells with 6 peptides derived from DNA topoisomerase-I protein were determined. Anti-nuclear antibodies (ANA) and anti-Scl-70 antibodies were determined by using the ELISA method. Results. In SSc patients, we detected a significantly higher number of IFN-γ- and IL-2-secreting CD8+ T cells than IFN-γ- and IL-2-secreting CD4+ T cells after stimulation with pooled peptides derived from DNA topoisomerase-I protein. A similar percentage of CD4+IL-2+, CD4+IFN-γ+, and CD8+IL-2+ were detected following stimulation with DNA topoisomerase-I protein -in SSc patients with anti-Scl-70 antibody (SSc/anti-Scl-70+) and those without. In contrast, the amount of CD8+IFN-γ+ cells was significantly higher in SSc/anti-Scl-70+ than those without. Stimulation with individual peptides showed that CSLRVEHINLHPELD (sPep3; 15 amino acids; position 505-519 of DNA topoisomerase-I protein) was the optimal epitope that induced T cells secreting the highest levels of IFN-γ and IL-2. A higher percentage of IFN-γ+CD4+ T cells was detected in SSc/anti-Scl-70+ than those without the following stimulation with peptides 2 (amino acid position 475-486 [RAVALYFIDKLA] of protein DNA topoisomerase). Conclusion. The results from this study emphasize the critical role of DNA topoisomerase-I peptides on the activation of T cells in SSc patients. The findings provide a better understanding of SSc’s immunopathogenesis and may lead to the development of diagnostic tools and specific treatments for SSc in the future.http://dx.doi.org/10.1155/2022/5072154
spellingShingle Oranit Likhit
Worawit Louthrenoo
Sa-nga Pattanakitsakul
Aroonroong Suttitheptumrong
Supot Hannongbua
Thanyada Rungrotmongkol
Hiroshi Noguchi
Fujio Takeuchi
Kobporn Boonnak
Determination of T Cell Responses in Thai Systemic Sclerosis Patients
Journal of Immunology Research
title Determination of T Cell Responses in Thai Systemic Sclerosis Patients
title_full Determination of T Cell Responses in Thai Systemic Sclerosis Patients
title_fullStr Determination of T Cell Responses in Thai Systemic Sclerosis Patients
title_full_unstemmed Determination of T Cell Responses in Thai Systemic Sclerosis Patients
title_short Determination of T Cell Responses in Thai Systemic Sclerosis Patients
title_sort determination of t cell responses in thai systemic sclerosis patients
url http://dx.doi.org/10.1155/2022/5072154
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