Interferon‐ γ ‐modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis

SUMMARY This study was designed to investigate the therapeutic effects of interferon (IFN)‐ γ ‐modulated dendritic cells (DC) in experimental autoimmune myasthenia gravis (EAMG). We induced EAMG in Lewis rats by immunization with Torpedo nicotinic acetylcholine receptor (nAChR) and adjuvant. On day 33 post‐immunization (p.i.), splenic DC were prepared, exposed to IFN‐ γ alone (IFN‐ γ ‐DC) or to IFN‐ γ in combination with 1‐methyl‐DL‐tryptophan (1‐MT), the specific inhibitor of indoleamine 2,3‐dioxygenase (IDO) (IFN‐ γ  + 1‐MT‐DC), and injected subcutaneously into rats with incipient EAMG on day 5 p.i. A control group of EAMG rats received naive DC on day 5 p.i., while another group received 1‐MT every other day, intraperitoneally (p.i.), from days 5 to 41 p.i. The severity of clinical signs of EAMG was reduced dramatically in IFN‐ γ ‐DC‐treated rats compared to rats receiving naive DC, IFN‐ γ  + 1‐MT‐DC or 1‐MT alone. The number of plasma cells secreting nAChR antibodies was reduced and the expression of B cell activation factor (BAFF) on splenic and lymph node mononuclear cells (MNC) was down‐regulated in rats treated with IFN‐ γ ‐DC. In vitro co‐culture of MNC derived from EAMG rats with IFN‐ γ ‐DC produced relatively few cells secreting nAChR antibodies. Addition of 1‐MT to the co‐culture significantly increased the number of cells secreting nAChR antibodies. We conclude that IFN‐ γ ‐DC reduced the number of plasma cells secreting nAChR antibodies in an IDO‐dependent manner and ameliorated the development of EAMG in Lewis rats.