Type II monocytes modulate T cell-mediated central nervous system autoimmune disease.
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.
Department of Neurology and Program in Immunology, University of California, San Francisco, 513 Parnassus Avenue, S-268, San Francisco, California 94143-0435, USA.
Martin S
MS
Weber
Thomas
T
Prod'homme
Sawsan
S
Youssef
Shannon E
SE
Dunn
Cynthia D
CD
Rundle
Linda
L
Lee
Juan C
JC
Patarroyo
Olaf
O
Stüve
Raymond A
RA
Sobel
Lawrence
L
Steinman
Scott S
SS
Zamvil
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000068717:Glatiramer Acetate; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000145:classification / Q000166:cytology* / Q000276:immunology*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D010455:Peptides; D000068717:Glatiramer Acetate