Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study

Publication

Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study

Journal Paper/Review - Jan 1, 2009

Putzki Norman, Kumar Manoj, Kreuzfelder Ernst, Grosse-Wilde Hans, Diener H C, Limmroth Volker

Citation

Putzki N, Kumar M, Kreuzfelder E, Grosse-Wilde H, Diener H, Limmroth V. Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study. European neurology 2009; 61:27-32.

Type

Journal Paper/Review (English)

Journal

European neurology 2009; 61

Publication Date

Jan 1, 2009

Issn Electronic

1421-9913

Pages

27-32

Brief description/objective

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.