Mitoxantrone Fails To Restore Impaired Suppressive Function of Regulatory T Cells in Multiple Sclerosis Patients

[P01.042] Mitoxantrone Fails To Restore Impaired Suppressive Function of Regulatory T Cells in Multiple Sclerosis Patients

Norman Putzki, Manoj Kumar, Erich Kreutzfelder, Volker Limmroth, Essen, Germany

OBJECTIVE: To examine if mitoxantrone restores the loss of suppressive activity of regulatory T cells in MS. BACKGROUND: CD4⁺CD25⁺ regulatory T cells (Tregs) play an important role in the control of autoimmunity by suppressing autoreactive T cells. We recently demonstrated that the suppressive function of Treg is impaired in MS patients. Disease modifying agents could theoretically restore the impaired suppressive function of Tregs. Mitoxantrone is a potent agent in the treatment of worsening MS. RESULTS: Stimulation with Myelin Basic Protein (MBP) and PWM led to significant proliferation of CD4⁺CD25^- in patients (n=20) and controls (n=20). Co-culturing of Tregs with CD4⁺CD25^- cells significantly (p < 0.05) reduced the MBP and PWM induced cell proliferation in controls (MBP: 37 % suppression; PMW: 41 % suppression). In MS patients, co-culturing lead to no suppression in MBP, in PWM suppression is significantly less pronounced (19 % suppression in MS vs. 41% in controls). When experiments were repeated every 3 months after initiation of mitoxantrone treatment (10mg/m2 every 3 months), we did not find significant differences in follow up examinations up to 12 months. CONCLUSIONS/RELEVANCE: The suppressive function of Tregs is impaired in MS patients. This suggests that a failure to maintain peripheral immune tolerance may be one of the critical factors for the development of CNS autoimmunity against myelin components. Mitoxantrone does not restore the impaired function of Tregs. Instead, our own investigations and those of others indicate that the predominant target of mitoxantrone are antigen presenting cells (i. e. B lymphocytes) inducing apoptosis.
Category - MS and Related Diseases
SubCategory - Basic Science

Tuesday, May 1, 2007 7:00 AM

Poster Sessions: Multiple Sclerosis and Related Diseases: Immunology I (7:00 AM-10:00 AM)

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