Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients.
Intravenous immunoglobulin (IVIg) preparations are reportedly effective in inhibiting the relapse of 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. In the 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. Using monocytes derived from healthy volunteers, 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 enhanced the expression of CD83, a marker of mature DCs (mDCs). Furthermore, IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 alpha4-integrin], the adhesion molecule required for mDCs to cross the blood-brain barrier. We obtained similar results on all the aforementioned cell surface molecules investigated in both healthy controls and MS patients. 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 differentiation, 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 to prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of immune cells into the central nervous system and affecting the cytokine profile.
Ohkuma
K
K
Therapeutic Protein Products Research Department, The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), Kumamoto, Japan.
Sasaki
T
T
Kamei
S
S
Okuda
S
S
Nakano
H
H
Hamamoto
T
T
Fujihara
K
K
Nakashima
I
I
Misu
T
T
Itoyama
Y
Y
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D039441:Integrin alpha4 / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*
D015703:Antigens, CD; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D016753:Interleukin-10; D039441:Integrin alpha4; D018664:Interleukin-12