Autoimmune Lymphoproliferative Syndrome-FAS Patients Have an Abnormal Regulatory T Cell (Treg) Phenotype but Display Normal Natural Treg-Suppressive Function on T Cell Proliferation

• Main Authors: Fabienne Mazerolles, Marie-Claude Stolzenberg, Olivier Pelle, Capucine Picard, Benedicte Neven, Alain Fischer, Aude Magerus-Chatinet, Frederic Rieux-Laucat
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-04-01
• Series: Frontiers in Immunology
• Subjects: human; autoimmune lymphoproliferative syndrome-FAS; cell proliferation; regulatory T cell; suppression assay
• Online Access: http://journal.frontiersin.org/article/10.3389/fimmu.2018.00718/full
• ISSN: 1664-3224

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.