Type II monocytes modulate T cell-mediated central nervous system autoimmune disease.

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 Med

journal_title

Nature medicine

authors

Weber MS,Prod'homme T,Youssef S,Dunn SE,Rundle CD,Lee L,Patarroyo JC,Stüve O,Sobel RA,Steinman L,Zamvil SS

doi

10.1038/nm1620

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

935-43

issue

8

eissn

1078-8956

issn

1546-170X

pii

nm1620

journal_volume

13

pub_type

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