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[sub.H]2 cells and CD4[sup.+]CD25[sup.+]FoxP3[sup.+] regulatory T cells (T[sub.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[sub.H]17 cell development and promoted both T[sub.H]2 differentiation and expansion of T[sub.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.
Author(s): Martin S Weber [1]; Thomas Prod'homme [1]; Sawsan Youssef [2]; Shannon E Dunn [2]; Cynthia D Rundle [1]; Linda Lee [1]; Juan C Patarroyo [1]; Olaf Stuve [3]; Raymond [...]