Multiple Sclerosis Patients Have Reduced Resting and Increased Activated CD4CD25FOXP3T Regulatory Cells

Resting and activated subpopulations of CD4CD25CD127T regulatory cells (Treg) and CD4CD25CD127 effector T cells in MS patients and in healthy individuals were compared. Peripheral blood mononuclear cells isolated using Ficoll Hypaque were stained with monoclonal antibodies and analysed by flow cytometer. CD45RA and Foxp3 expression within CD4 cells and in CD4CD25CD127T cells identified Population I; CD45RAFoxp3, Population II; CD45RAFoxp3 and Population III; CD45RAFoxp3 cells. Effector CD4CD127 T cells were subdivided into Population IV; memory /effector CD45RA CD25Foxp3 and Population V; effector naïve CD45RACD25Foxp3CCR7 and terminally differentiated RA (TEMRA) effector memory cells. Chemokine receptor staining identified CXCR3Th1-like Treg, CCR6Th17-like Treg and CCR7 resting Treg. Resting Treg (Population I) were reduced in MS patients, both in untreated and treated MS compared to healthy donors. Activated/memory Treg (Population II) were significantly increased in MS patients compared to healthy donors. Activated effector CD4 (Population IV) were increased and the naïve/ TEMRA CD4 (Population V) were decreased in MS compared to HD. Expression of CCR7 was mainly in Population I, whereas expression of CCR6 and CXCR3 was greatest in Populations II and intermediate in Population III. In MS, CCR6Treg were lower in Population III. This study found MS is associated with significant shifts in CD4T cells subpopulations. MS patients had lower resting CD4CD25CD45RACCR7 Treg than healthy donors while activated CD4CD25CD45RAFoxp3Treg were increased in MS patients even before treatment. Some MS patients had reduced CCR6Th17-like Treg, which may contribute to the activity of MS.