Expansion of regulatory T cells in patients with Langerhans cell histiocytosis.
Langerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of L...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-08-01
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| Series: | PLoS Medicine |
| Online Access: | http://europepmc.org/articles/PMC1945037?pdf=render |
| _version_ | 1818939831882874880 |
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| author | Brigitte Senechal Gaelle Elain Eric Jeziorski Virginie Grondin Natacha Patey-Mariaud de Serre Francis Jaubert Kheira Beldjord Arielle Lellouch Christophe Glorion Michel Zerah Pierre Mary Mohammed Barkaoui Jean Francois Emile Liliane Boccon-Gibod Patrice Josset Marianne Debré Alain Fischer Jean Donadieu Frederic Geissmann |
| author_facet | Brigitte Senechal Gaelle Elain Eric Jeziorski Virginie Grondin Natacha Patey-Mariaud de Serre Francis Jaubert Kheira Beldjord Arielle Lellouch Christophe Glorion Michel Zerah Pierre Mary Mohammed Barkaoui Jean Francois Emile Liliane Boccon-Gibod Patrice Josset Marianne Debré Alain Fischer Jean Donadieu Frederic Geissmann |
| author_sort | Brigitte Senechal |
| collection | DOAJ |
| description | Langerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas. The present study was designed to further investigate the nature of proliferating cells and the immune mechanisms involved in the LCH granulomas.Biopsies (n = 24) and/or blood samples (n = 25) from 40 patients aged 0.25 to 13 y (mean 7.8 y), were studied to identify cells that proliferate in blood and granulomas. We found that the proliferating index of LCs was low ( approximately 1.9%), and we did not observe expansion of a monocyte or dendritic cell compartment in patients. We found that LCH lesions were a site of active inflammation, tissue remodeling, and neo-angiogenesis, and the majority of proliferating cells were endothelial cells, fibroblasts, and polyclonal T lymphocytes. Within granulomas, interleukin 10 was abundant, LCs expressed the TNF receptor family member RANK, and CD4(+) CD25(high) FoxP3(high) regulatory T cells (T-regs) represented 20% of T cells, and were found in close contact with LCs. FoxP3(+) T-regs were also expanded compared to controls, in the blood of LCH patients with active disease, among whom seven out of seven tested exhibited an impaired skin delayed-type hypersensitivity response. In contrast, the number of blood T-regs were normal after remission of LCH.These findings indicate that LC accumulation in LCH results from survival rather than uncontrolled proliferation, and is associated with the expansion of T-regs. These data suggest that LCs may be involved in the expansion of T-regs in vivo, resulting in the failure of the host immune system to eliminate LCH cells. Thus T-regs could be a therapeutic target in LCH. |
| first_indexed | 2024-12-20T06:30:00Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-20T06:30:00Z |
| publishDate | 2007-08-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-ff2ec71f740746549b4d4a1445487e0c2022-12-21T19:50:11ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762007-08-0148e25310.1371/journal.pmed.0040253Expansion of regulatory T cells in patients with Langerhans cell histiocytosis.Brigitte SenechalGaelle ElainEric JeziorskiVirginie GrondinNatacha Patey-Mariaud de SerreFrancis JaubertKheira BeldjordArielle LellouchChristophe GlorionMichel ZerahPierre MaryMohammed BarkaouiJean Francois EmileLiliane Boccon-GibodPatrice JossetMarianne DebréAlain FischerJean DonadieuFrederic GeissmannLangerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas. The present study was designed to further investigate the nature of proliferating cells and the immune mechanisms involved in the LCH granulomas.Biopsies (n = 24) and/or blood samples (n = 25) from 40 patients aged 0.25 to 13 y (mean 7.8 y), were studied to identify cells that proliferate in blood and granulomas. We found that the proliferating index of LCs was low ( approximately 1.9%), and we did not observe expansion of a monocyte or dendritic cell compartment in patients. We found that LCH lesions were a site of active inflammation, tissue remodeling, and neo-angiogenesis, and the majority of proliferating cells were endothelial cells, fibroblasts, and polyclonal T lymphocytes. Within granulomas, interleukin 10 was abundant, LCs expressed the TNF receptor family member RANK, and CD4(+) CD25(high) FoxP3(high) regulatory T cells (T-regs) represented 20% of T cells, and were found in close contact with LCs. FoxP3(+) T-regs were also expanded compared to controls, in the blood of LCH patients with active disease, among whom seven out of seven tested exhibited an impaired skin delayed-type hypersensitivity response. In contrast, the number of blood T-regs were normal after remission of LCH.These findings indicate that LC accumulation in LCH results from survival rather than uncontrolled proliferation, and is associated with the expansion of T-regs. These data suggest that LCs may be involved in the expansion of T-regs in vivo, resulting in the failure of the host immune system to eliminate LCH cells. Thus T-regs could be a therapeutic target in LCH.http://europepmc.org/articles/PMC1945037?pdf=render |
| spellingShingle | Brigitte Senechal Gaelle Elain Eric Jeziorski Virginie Grondin Natacha Patey-Mariaud de Serre Francis Jaubert Kheira Beldjord Arielle Lellouch Christophe Glorion Michel Zerah Pierre Mary Mohammed Barkaoui Jean Francois Emile Liliane Boccon-Gibod Patrice Josset Marianne Debré Alain Fischer Jean Donadieu Frederic Geissmann Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Medicine |
| title | Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. |
| title_full | Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. |
| title_fullStr | Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. |
| title_full_unstemmed | Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. |
| title_short | Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. |
| title_sort | expansion of regulatory t cells in patients with langerhans cell histiocytosis |
| url | http://europepmc.org/articles/PMC1945037?pdf=render |
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