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* Department of Neurology and Rehabilitation,
Department of Microbiology and Immunology, and
Department of Surgery; University of Illinois, Chicago, IL 60612
Dendritic cells (DCs) have the potential to activate or tolerize T cells in an Ag-specific manner. Although the precise mechanism that determines whether DCs exhibit tolerogenic or immunogenic functions has not been precisely elucidated, growing evidence suggests that DC function is largely dependent on differentiation status, which can be manipulated using various growth factors. In this study, we investigated the effects of mobilization of specific DC subsets—using GM-CSF and fms-like tyrosine kinase receptor 3-ligand (Flt3-L)—on the susceptibility to induction of experimental autoimmune myasthenia gravis (EAMG). We administered GM-CSF or Flt3-L to C57BL/6 mice before immunization with acetylcholine receptor (AChR) and observed the effect on the frequency and severity of EAMG development. Compared with AChR-immunized controls, mice treated with Flt3-L before immunization developed EAMG at an accelerated pace initially, but disease frequency and severity was comparable at the end of the observation period. In contrast, GM-CSF administered before immunization exerted a sustained suppressive effect against the induction of EAMG. This suppression was associated with lowered serum autoantibody levels, reduced T cell proliferative responses to AChR, and an expansion in the population of FoxP3+ regulatory T cells. These results highlight the potential of manipulating DCs to expand regulatory T cells for the control of autoimmune diseases such as MG.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grant 1RO1 AI058290–01 (to B.S.P.).
2 Address correspondence and reprint requests to Dr. Matthew N. Meriggioli, Department of Neurology and Rehabilitation, University of Illinois, 912 South Wood Street, 855N, M/C 796, Chicago, IL 60612. E-mail address: mmerig{at}uic.edu
3 Abbreviations used in this paper: MG, myasthenia gravis; AChR, acetylcholine receptor; DC, dendritic cell; Flt3-L, fms-like tyrosine kinase receptor 3-ligand; tAChR, torpedo AChR; Treg, regulatory T cell; EAMG, experimental autoimmune MG; NMJ, neuromuscular junction; EAT, experimental autoimmune thyroiditis.
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