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)-beta, 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(H)2 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(H)17 cell development and promoted both T(H)2 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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Weber MS,Prod'homme T,Youssef S,Dunn SE,Rundle CD,Lee L,Patarroyo JC,Stüve O,Sobel RA,Steinman L,Zamvil SSdoi
10.1038/nm1620subject
Has Abstractpub_date
2007-08-01 00:00:00pages
935-43issue
8eissn
1078-8956issn
1546-170Xpii
nm1620journal_volume
13pub_type
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