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

摘要

Objective Autoimmune 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. Results The proportion of CD25~(high)CD127~(low)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 CD25~(high)FOXP3~(+)Helios~(+)T cells. The ALPS patients also displayed a high proportion of na?ve Treg (FOXP3~(low)CD45RA~(+)) and an unusual subpopulation (CD4~(+)CD127~(low)CD15s~(+)CD45RA~(+)). Despite this abnormal phenotype, the CD25~(high)CD127~(low)Tregs’ suppressive function was unaffected. Furthermore, conventional T cells from FAS -mutated patients showed normal levels of sensitivity to Treg suppression. Conclusion An 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.