Mitoxantrone Does Not Restore the Impaired Suppressive Function of Natural Regulatory T Cells in Patients Suffering from Multiple Sclerosis

CD4+CD25+ regulatory T (T reg ) cells play a major role in controlling autoimmunity by suppressing self-reactive T cells. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system, where T cells are of major importance. T reg cell frequency and function are potential therapeutic targets of MS treatment. Mitoxantrone (MX) is a potent immunosuppressant for the treatment of active MS. We investigated the long-term effects of MX on the suppressive function of T reg after mitogen and myelin basic protein (MBP) stimulation in 20 MX-treated patients. MX therapy did not restore the reduced suppressive activity of a mixture of CD25 intermediate or CD25 high expressing T reg (healthy controls, MBP: 37.3%; MS patients, MBP: –1.9 vs. 6.6% suppression after MX treatment for 6 months, p > 0.2). The frequency of T reg cells was not affected by MX. A single infusion of MX (10 mg/m 2 body surface) induced a selective and persistent reduction of approximately 30% of absolute and relative counts of B lymphocytes (p < 0.05). MX therapy does not influence T reg cell frequency or function. MX seems to exhibit its efficacy in MS mainly by a suppression of humoral immunity.