Natural naive regulatory T cell development and function are disturbed in multiple sclerosis patients

Abstract

Background: Myelin-reactive T cells may play a pathogenic role in multiple sclerosis (MS). We and others have shown that regulatory CD4+CD25+FOXP3+CD127low T cells (Tregs) are functionally disturbed in relapsing-remitting (RR) MS patients but not in secondary progressive (SP) MS patients. Objective: To clarify this difference in Treg activity between early and chronic disease stages in MS. Methods: We analyzed the functional capacity and homeostatic parameters of (precursor) naive Tregs (nTregs) and memory Tregs (mTregs). We also measured myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) proliferative responses of CD4total T cells (including Tregs), naive (CD45RAhigh) and memory (CD45RA-) CD4+CD25-CD127high T cells (no Tregs included) of RRMS and SPMS patients and healthy controls (HC) by means of a CFSE dilution assay and measured cytokine production of the myelinreactive T cells. Results: The suppressive capacity of FACS-sorted nTregs was impaired in both early and chronic MS patients, whereas only the latter group showed a restored mTreg function. Chronic MS patients had increased numbers of mTregs as compared with agematched early MS patients, whereas nTreg frequencies did not differ.