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Mechanism of biocompatible microcapsules in vitro immune adjuvant

Author: SunHongFan
Tutor: SongCunXian
School: Peking Union Medical College , China
Course: Biomedical Engineering
Keywords: Adjuvant Dendritic cell Antigen presentation
CLC: R392
Type: Master's thesis
Year: 2008
Downloads: 82
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Abstract


As the most important antigen presenting cells, dendritic cells (DCs) are likely to play a significant role in the induction of immune responses in vivo. Mature DC express high levels of major histocompatibility complex (MHC) class II and co-stimulatory molecules, such as CD40, CD80 and CD86, and thus provide signals required for T-cell activation. DCs have been referred to as "nature’s adjuvants" .The central role played by DCs suggests that many adjuvants may function via effects on this cell population. However, the ability to induce DC activation has only been defined for a few adjuvant formulations, particularly those derived from bacteria.This report studied the effects of adjuvant formulations on the activation and antigen-presenting functions of bone marrow-derived dendritic cells (BM-DCs). While LPS could induce high-level expression of MHC Class II and co-stimulator molecules on DCs, it did not enhance antigen presentation to co-stimulation independent DO11.GFP T hybridoma cells. In contrast, alum, NISV and PLGA formulations failed to activate DCs, but NISV and PLGA could enhance antigen-presentation efficiency by 10 - 100-fold. Irrespective of the previously described antigen release characteristics of each adjuvant, antigen presentation peaked at 6 h and waned thereafter for all formulations.Given the importance of DCs in the activation of native T cell responses, these studies suggest that as yet undefined pathways of DC activation in vivo may underlie the activity of alum, PLGA and NISV adjuvants. The ability of these particulate systems to induce high levels of antigen presentation by DCs probably has a more significant role in their adjuvant activity.

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