The limitation of IL-10-exposed dendritic cells in the treatment of experimental autoimmune myasthenia gravis and myasthenia gravis.
Dendritic cells (DC) are highly specialized antigen presenting cells that play critical roles as instigators and regulators of immune responses including B cell function, antibody synthesis and isotype switch. In this study, we compared immunotherapeutic effect of IL-10-treated DC (IL-10-DC) via both intraperitoneal (i.p.) and subcutaneous (s.c.) delivery in rats with incipient experimental autoimmune myasthenia gravis (EAMG). Spleen DC were isolated from onset of EAMG on day 39 post-immunization, exposed in vitro to IL-10, and then injected into incipient EAMG at dose of 1 x 10(6) cells/rat on day 5 after immunization. Intraperitoneal administration of IL-10-DC suppressed clinical scores, anti-acetylcholine receptors (AChR) antibody secreting cells, antigen-specific IL-10/IFN-gamma production and T cell proliferation compared to control EAMG rats. Importantly, IL-10-DC, if given by s.c. route, failed to ameliorate clinical sign of EAMG. Simultaneously, T cell proliferation, anti-AChR antibody secreting cells and IL-10/IFN-gamma production had no alteration, as compared to control EAMG rats. Both in vitro and in vivo experiments showed that treatment of IL-10 inhibited the migration of DC toward MIP-3beta and lymph node, indicating that in vitro manipulation of DC with IL-10 alters the migration of DC that influences the therapeutic effect in the treatment of autoimmune diseases. In MG patients, neither the improvement of clinical symptom nor the alteration of immunological parameter was observed through s.c. delivery of IL-10-DC, suggesting the limitation of IL-10-DC in the treatment of MG patients.
Xiao
Bao-Guo
BG
Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China. bgxiao@shmu.edu.cn
Duan
Rui-Sheng
RS
Zhu
Wen-Hua
WH
Lu
Chuan-Zhen
CZ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D016753:Interleukin-10; D007371:Interferon-gamma