Improved Stimulation of Human Dendritic Cells by Receptor Engagement with Surface-modified Microparticles

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Abstract
Dendritic cells (DC) need to be stimulated before they can function to initiate immune responses. This study investigates whether microparticles loaded with antibodies specific for selected receptors expressed by DC can induce stimulation of these cells. Plain microparticles were compared with microparticles which were surface-loaded with specific antibodies for human CD40, Fcγ, αvβ3 and αvβ5 integrin receptors. The antibodies were either physically adsorbed or covalently linked to the microparticle surface. Anti-CD40 antibody and human IgG immobilised on the surface of microparticles induced enhanced DC maturation and activation as expressed by CD83 and CD86 up-regulation. IL-12 secretion was induced at a detectable but relatively low level. Both anti-integrin antibodies (anti-αvβ3 and anti-αvβ5) induced comparable and considerable maturation of DC, but only anti-αvβ3 antibody induced significant activation of DC, whereas anti-αvβ5 did not. The stimulatory effects were most pronounced by employing microparticles with covalently linked antibodies, but were also observed to a minor extent when the antibodies were physically adsorbed to polystyrene and biodegradable poly(lactide-co-glycolide) microparticles. Engineering of microparticles by surface conjugation of specific ligands to stimulate DC may increase the effectiveness of microparticulate vaccine delivery systems.