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Interferon-gamma-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis
- Adikari, SB (author)
- Lian, H (author)
-
- Link, H (author)
- Karolinska Institutet
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- Huang, YM (author)
- Xiao, BG (author)
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- (creator_code:org_t)
- 2004-10-07
- 2004
- English.
- In: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:2, s. 230-236
- Journal article (peer-reviewed)
Abstract
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- 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.
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