Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function.
Background The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. Methods A longit...
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ftdoajarticles:oai:doaj.org/article:0f05e2586303427a9298d1232c98812f 2023-05-15T15:18:37+02:00 Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. Edessa Negera Kidist Bobosha Abraham Aseffa Hazel M Dockrell Diana N J Lockwood Stephen L Walker 2022-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010641 https://doaj.org/article/0f05e2586303427a9298d1232c98812f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010641 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010641 https://doaj.org/article/0f05e2586303427a9298d1232c98812f PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010641 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010641 2022-12-30T20:23:03Z Background The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. Methods A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. Results 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. Conclusion The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 7 e0010641 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Edessa Negera Kidist Bobosha Abraham Aseffa Hazel M Dockrell Diana N J Lockwood Stephen L Walker Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. Methods A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. Results 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. Conclusion The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our ... |
format |
Article in Journal/Newspaper |
author |
Edessa Negera Kidist Bobosha Abraham Aseffa Hazel M Dockrell Diana N J Lockwood Stephen L Walker |
author_facet |
Edessa Negera Kidist Bobosha Abraham Aseffa Hazel M Dockrell Diana N J Lockwood Stephen L Walker |
author_sort |
Edessa Negera |
title |
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
title_short |
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
title_full |
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
title_fullStr |
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
title_full_unstemmed |
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function. |
title_sort |
regulatory t cells in erythema nodosum leprosum maintain anti-inflammatory function. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010641 https://doaj.org/article/0f05e2586303427a9298d1232c98812f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 7, p e0010641 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010641 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010641 https://doaj.org/article/0f05e2586303427a9298d1232c98812f |
op_doi |
https://doi.org/10.1371/journal.pntd.0010641 |
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PLOS Neglected Tropical Diseases |
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16 |
container_issue |
7 |
container_start_page |
e0010641 |
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