Details

Autor(en) / Beteiligte

• Papenfuss, Tracey L.
• Kithcart, Aaron P.
• Powell, Nicole D.
• McClain, Melanie A.
• Gienapp, Ingrid E.
• Shawler, Todd M.
• Whitacre, Caroline C.

Titel

A novel approach to generating disease modifying dendritic cells (DCs) (129.13)

Ist Teil von

• The Journal of immunology (1950), 2007-04, Vol.178 (1_Supplement), p.S220-S220

Erscheinungsjahr

2007

Quelle

EZB*

Beschreibungen/Notizen

• Abstract Dendritic cells (DCs) bridge the innate and adaptive immune responses and DC immunotherapy has shown promise in the treatment of transplantation, allergic and autoimmune diseases. One primary limitation in studying and utilizing DCs is their small numbers in vivo. While the growth factor Flt3-ligand (FL) is used to expand DCs in vivo, GM-CSF is predominantly used to generate DCs in vitro from bone marrow (BM-DC). The purpose of this study was to explore the use of murine FL (mFL), the mouse homologue of human FL, to generate DCs in vitro. In vivo (tumor-based) mFL delivery reliably expanded splenic DCs comparable to hFL In vitro BM-DCs generated with mFL were more similar to hFL than GM-CSF derived BM-DCs and appeared to be immature. Specifically, CD11c, CD11b and maturation markers CD80 and CD86 were lower in mFL and hFL versus GM-CSF BM-DCs. Maturation of mFL BM-DCs with TNF-α±LPS increased CD80, CD86 and CD40 expression. Transfer of matured mFL BM-DCs to mice prior to immunization with myelin oligodendrocyte glycoprotein (MOG35-55) significantly increased cumulative disease (26.79±10.12) and peak disease scores (3.07±1.16) compared to immature mFL BM-DCs (20.21 ±7.64 and 1.86±0.7, respectively). These results suggest that exposure to mFL in vitro is a novel method to generate large numbers of immature BM-DCs which can modulate the course of autoimmune disease. (Support: NIH AI-43376, K01 R022198 and NMSS RG3272).