Abstract

Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-, and decreased production of IL-12 and tumor necrosis factor (TNF). This anti-inflammatory cytokine shift was associated with reduced STAT-1 signaling. Type II monocytes directed differentiation of T_H2 cells and CD4⁺CD25⁺FoxP3⁺ regulatory T cells (T_reg) independent of antigen specificity. Type II monocyte–induced regulatory T cells specific for a foreign antigen ameliorated experimental autoimmune encephalomyelitis (EAE), indicating that neither GA specificity nor recognition of self-antigen was required for their therapeutic effect. Adoptive transfer of type II monocytes reversed EAE, suppressed T_H17 cell development and promoted both T_H2 differentiation and expansion of T_reg cells in recipient mice. This demonstration of adoptive immunotherapy by type II monocytes identifies a central role for these cells in T cell immune modulation of autoimmunity.

1. Department of Neurology and Program in Immunology, University of California, San Francisco, 513 Parnassus Avenue, S-268, San Francisco, California 94143-0435, USA.
2. Department of Neurology and Neurological Sciences, Interdepartmental Program in Immunology, Stanford University, Stanford, California, USA.
3. Neurology Section, Veterans Affairs North Texas Health Care System, Medical Service, Dallas, Texas, USA.
4. Department of Pathology, Stanford University, Stanford, California, USA.

Correspondence to: Scott S Zamvil¹ e-mail: zamvil@ucsf.neuroimmunol.org

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