Circulating CD4+CD25+ and CD4+CD25+ T cells in myasthenia gravis and in relation to thymectomy

Studies in experimental animal models of human autoimmune diseases have revealed that CD4⁺CD25⁺ T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto‐aggressive immunity. Myasthenia gravis (MG) is the best‐characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4⁺CD25⁺ versus CD4⁺CD25^– cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4⁺CD25⁺ cells. CD4⁺CD25^high cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4⁺CD25^high cells were similar in MG patients irrespective of treatment with thymectomy. CD4⁺CD25⁺ cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4⁺CD25^– cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)‐DR‐positive cells. In both MG patients and HCs, CD4⁺CD25⁺ cells also contained a high proportion of CD95‐expressing cells as possible evidence of apoptosis‐proneness. Upon stimulation with anti‐CD3/CD28 monoclonal antibodies, CD4⁺CD25⁺ cells responded more vigorously than CD4⁺CD25^– cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4⁺CD25^– cells are mainly naïve T cells, in non‐thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA‐DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4⁺CD25⁺ cells in MG, nor is the proportion of CD4⁺CD25⁺ cells influenced by thymectomy.