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

CD4+CD25+ regulatory T (Treg) 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. Treg 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 Treg 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 CD25intermediate or CD25high expressing Treg (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 Treg cells was not affected by MX. A single infusion of MX (10 mg/m2 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 Treg cell frequency or function. MX seems to exhibit its efficacy in MS mainly by a suppression of humoral immunity

CD4 +CD25 +FoxP3 + T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4 +CD25 +FoxP3 + regulatory T cell (T reg) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25 high and CD25 intemediate expressing T reg cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly ( p < 0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T reg counts was significantly increased in MS patients (mean ± S.D.; 20 ± 8%) compared with healthy individuals (15 ± 5%). These findings suggest that impaired T reg function may be involved in pathogenesis of MS