J Immunol 2003 May 1;170(9):4483-8
Vieira PL, Heystek HC, Wormmeester J, Wierenga EA, Kapsenberg ML.
Departments of. Cell Biology and Histology and. Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Glatiramer acetate (GA; copolymer-1, Copaxone) suppresses the induction of experimental autoimmune encephalomyelitis and reduces the relapse frequency in relapsing-remitting multiple sclerosis.
Although it has become clear that GA induces protective degenerate Th2/IL-10 responses, its precise mode of action remains elusive.
Because the cytokine profile of Th cells is often regulated by dendritic cells (DC), we studied the modulatory effects of GA on the T cell regulatory function of human DC.
This study shows the novel selective inhibitory effect of GA on the production of DC-derived inflammatory mediators without affecting DC maturation or DC immunostimulatory potential.
DC exposed to GA have an impaired capacity to secrete the major Th1 polarizing factor IL-12p70 in response to LPS and CD40 ligand triggering.
DC exposed to GA induce effector IL-4-secreting Th2 cells and enhanced levels of the anti-inflammatory cytokine IL-10.
The anti-inflammatory effect of GA is mediated via DC as GA does not affect the polarization patterns of naive Th cells activated in an APC-free system.
Together, these results reveal that APC are essential for the GA-mediated shift in the Th cell profiles and indicate that DC are a prime target for the immunomodulatory effects of GA.