Protective potential of experimental autoimmune myasthenia gravis in Lewis rats by IL-10-modified dendritic cells.
Dendritic cells (DC) are usually regarded as antigen-presenting cells (APC) involved in T cell activation, but DC also directly or indirectly affect B cell function, antibody synthesis and isotype switch. In this study, we explore potential of DC-based immunotherapy in ongoing experimental autoimmune myasthenia gravis (EAMG) in Lewis rats, which is mediated by anti-acetylcholine receptor (AChR) antibodies. Spleen DC were isolated from onset of Lewis rat EAMG on day 39 post immunization (p.i.), exposed in vitro to IL-10 and then injected intraperitoneally into ongoing EAMG Lewis rats at dose of 1 x 10(6) cells/rat on day 5 p.i. with AChR + complete Freund's adjuvant. IL-10-modified DC resulted in lower clinical scores, less body weight loss, lower numbers of anti-AChR IgG antibody-secreting cells and lower affinity of anti-AChR antibodies in rats receiving IL-10-modified DC, accompanied with lower expression of CD80 and CD86 and lower lymphocyte proliferation among lymph node mononuclear cells compared with control EAMG rats. Lower levels of IL-10 and IFN-gamma were also found in the supernatants of AChR-stimulated lymph node MNC culture in rats receiving IL-10-modified DC. These results demonstrate that IL-10-modified DC induced hypo-responsiveness by down-regulating co-stimulatory molecules, and reduced production of anti-AChR antibodies possibly by inhibiting IL-10 production. Importantly, this procedure that autologous DC from EAMG were adopted to treat ongoing EAMG is more close to clinical trial in human, encouraging future evaluation in human myasthenia gravis.
Duan
Rui-Sheng
RS
Division of Neuroimmunology, Neurotec, Karolinska Institute, Stockholm, Sweden.
Adikari
Sanjaya Bandara
SB
Huang
Yu-Min
YM
Link
Hans
H
Xiao
Bao-Guo
BG
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014101:Torpedo
D001323:Autoantibodies; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma