Induction of peripheral tolerance to experimental autoimmune myasthenia gravis by acetylcholine receptor-pulsed dendritic cells.
Dendritic cells (DC) are usually regarded as antigen-presenting cells involved in T cell activation, but DC also directly and indirectly affect B cell activation, antibody synthesis, and isotype switch. In the present study, bone marrow (BM)-derived DC from healthy rats were pulsed in vitro with acetylcholine receptor (AChR) and injected subcutaneously into healthy Lewis rats. No clinical signs of the first phase of experimental autoimmune myasthenia gravis (EAMG) were observed during 3 weeks of observation. Upon immunization with AChR and complete Freund's adjuvant, the rats that had received AChR-pulsed DC did not develop clinical EAMG. This tolerance of rats injected with AChR-pulsed DC was associated with reduced expression of B cell-activating factor (BAFF) and by reduced numbers of B cells among splenic mononuclear cells (MNC) compared to rats injected with medium or unpulsed DC. Anti-AChR IgG antibody-secreting cells were decreased, while the ratio of IgG1:IgG2b isotypes was enhanced in rats treated with AChR-pulsed DC compared to control EAMG rats. These results demonstrate that AChR-pulsed DC induce peripheral tolerance to EAMG by possibly inhibiting the expression of BAFF and production of anti-AChR antibodies, providing a possible potential for immunotherapy of antibody-mediated autoimmune diseases.
Xiao
Bao-Guo
BG
NEUROTEC Department, Karolinska Institute, Alfred Nobels Alle 10, SE-141 83, Stockholm, Sweden. bao-guo.xiao@neutrotec.ki.se
Duan
Rui-Sheng
RS
Link
Hans
H
Huang
Yu-Min
YM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*
D018122:B7-1 Antigen; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic