Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation
ObjectiveAutoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTre...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00718/full |
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doaj-5d860a781cf64d7bb1b6f11dfc9c80a1 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Fabienne Mazerolles Fabienne Mazerolles Marie-Claude Stolzenberg Marie-Claude Stolzenberg Olivier Pelle Olivier Pelle Capucine Picard Capucine Picard Capucine Picard Capucine Picard Benedicte Neven Benedicte Neven Benedicte Neven Alain Fischer Alain Fischer Alain Fischer Aude Magerus-Chatinet Aude Magerus-Chatinet Frederic Rieux-Laucat Frederic Rieux-Laucat |
| spellingShingle |
Fabienne Mazerolles Fabienne Mazerolles Marie-Claude Stolzenberg Marie-Claude Stolzenberg Olivier Pelle Olivier Pelle Capucine Picard Capucine Picard Capucine Picard Capucine Picard Benedicte Neven Benedicte Neven Benedicte Neven Alain Fischer Alain Fischer Alain Fischer Aude Magerus-Chatinet Aude Magerus-Chatinet Frederic Rieux-Laucat Frederic Rieux-Laucat Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation Frontiers in Immunology human autoimmune lymphoproliferative syndrome-FAS cell proliferation regulatory T cell suppression assay |
| author_facet |
Fabienne Mazerolles Fabienne Mazerolles Marie-Claude Stolzenberg Marie-Claude Stolzenberg Olivier Pelle Olivier Pelle Capucine Picard Capucine Picard Capucine Picard Capucine Picard Benedicte Neven Benedicte Neven Benedicte Neven Alain Fischer Alain Fischer Alain Fischer Aude Magerus-Chatinet Aude Magerus-Chatinet Frederic Rieux-Laucat Frederic Rieux-Laucat |
| author_sort |
Fabienne Mazerolles |
| title |
Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation |
| title_short |
Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation |
| title_full |
Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation |
| title_fullStr |
Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation |
| title_full_unstemmed |
Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation |
| title_sort |
autoimmune lymphoproliferative syndrome-fas patients have an abnormal regulatory t cell (treg) phenotype but display normal natural treg-suppressive function on t cell proliferation |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2018-04-01 |
| description |
ObjectiveAutoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS.ResultsThe proportion of CD25highCD127low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3+CD4+ T cells from ALPS patients and thus an abnormally low proportion of CD25highFOXP3+ Helios+ T cells. The ALPS patients also displayed a high proportion of naïve Treg (FOXP3lowCD45RA+) and an unusual subpopulation (CD4+CD127lowCD15s+CD45RA+). Despite this abnormal phenotype, the CD25highCD127low Tregs’ suppressive function was unaffected. Furthermore, conventional T cells from FAS-mutated patients showed normal levels of sensitivity to Treg suppression.ConclusionAn abnormal Treg phenotype is observed in circulating lymphocytes of ALPS patients. However, these Tregs displayed a normal suppressive function on T effector proliferation in vitro. This is suggesting that lymphoproliferation observed in ALPS patients does not result from Tregs functional defect or T effector cells insensitivity to Tregs suppression. |
| topic |
human autoimmune lymphoproliferative syndrome-FAS cell proliferation regulatory T cell suppression assay |
| url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00718/full |
| work_keys_str_mv |
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doaj-5d860a781cf64d7bb1b6f11dfc9c80a12020-11-24T23:15:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00718308775Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell ProliferationFabienne Mazerolles0Fabienne Mazerolles1Marie-Claude Stolzenberg2Marie-Claude Stolzenberg3Olivier Pelle4Olivier Pelle5Capucine Picard6Capucine Picard7Capucine Picard8Capucine Picard9Benedicte Neven10Benedicte Neven11Benedicte Neven12Alain Fischer13Alain Fischer14Alain Fischer15Aude Magerus-Chatinet16Aude Magerus-Chatinet17Frederic Rieux-Laucat18Frederic Rieux-Laucat19INSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FranceINSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FranceINSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceINSERM UMR1163, Cell Sorting Facility, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FrancePaediatric Haematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique—Hôpitaux de Paris (APHP), Paris, FranceCenter for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, APHP, Paris, FranceLaboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, University Paris Descartes Sorbonne Paris Cité, Paris, FranceINSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FrancePaediatric Haematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique—Hôpitaux de Paris (APHP), Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FrancePaediatric Haematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique—Hôpitaux de Paris (APHP), Paris, FranceCollège de France, Paris, FranceINSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FranceINSERM UMR1163, Laboratory of Immunogenetics of Paediatric Autoimmunity, Paris, FranceParis Descartes—Sorbonne Paris Cité University, Imagine Institute Paris, Paris, FranceObjectiveAutoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS.ResultsThe proportion of CD25highCD127low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3+CD4+ T cells from ALPS patients and thus an abnormally low proportion of CD25highFOXP3+ Helios+ T cells. The ALPS patients also displayed a high proportion of naïve Treg (FOXP3lowCD45RA+) and an unusual subpopulation (CD4+CD127lowCD15s+CD45RA+). Despite this abnormal phenotype, the CD25highCD127low Tregs’ suppressive function was unaffected. Furthermore, conventional T cells from FAS-mutated patients showed normal levels of sensitivity to Treg suppression.ConclusionAn abnormal Treg phenotype is observed in circulating lymphocytes of ALPS patients. However, these Tregs displayed a normal suppressive function on T effector proliferation in vitro. This is suggesting that lymphoproliferation observed in ALPS patients does not result from Tregs functional defect or T effector cells insensitivity to Tregs suppression.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00718/fullhumanautoimmune lymphoproliferative syndrome-FAScell proliferationregulatory T cellsuppression assay |