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Published on: August 13, 2013
Alterations of Thymus-Derived Tregs in Multiple Sclerosis
Tiziana Lorenzini1, Wolfgang Faigle1, Josefine Ruder1
1From the Neuroimmunology and MS Research (T.L., W.F., J.R., M.J.D., R.M.), Neurology Clinic, University Hospital Zurich; Division of Immunology (T.L.), University Children's Hospital Zurich, University of Zurich; Cellerys AG (W.F., R.M.), Schlieren, Switzerland; Immunity and Cancer (U932) (W.F.), Immune Response to Cancer Laboratory, Institut Curie, 26 rue d'Ulm, CEDEX 05, Paris, France; Functional Genomics Center Zurich (L.O.), Swiss Federal Institute of Technology and University of Zurich; Institute of Experimental Immunology (R.M.), University of Zurich, Switzerland; and Therapeutic Design Unit (R.M.), Center for Molecular Medicine, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Background And Objectives:
Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear.
Methods:
By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors.
Results:
Patients with MS showed a reduced frequency of CD4+ T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs.
Discussion:
Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.
