A Study of the Regulation of Dendritic Cells and Immunological Memory by Immunoglobulins in Multiple Sclerosis

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Intravenous immunoglobulin preparations (IVIg) are reportedly effective in inhibiting the relapseof multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. Using a system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of Immunoglobulin G (IgG) on these antigen-presenting cells. Treatment of monocytes derived from a healthy volunteer with IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG treatment enhanced the expression of CD83, a marker of mature DCs (mDCs). IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 〓4-integrin], the adhesion molecule required for mDCs to cross the blood brain barrier (BBB). As neutralizing antibodies against CD49d have a therapeutic effect on MS, we investigated the effect of IgG on Mo-DCs derived from the peripheral blood of relapsing-remitting MS patients. We obtained similar results in both MS patients and healthy controls. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC maturation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of the central nervous system and affecting the cytokine profile.