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Nanoparticles Targeting Dendritic Cell Surface Molecules Effectively Block T cell Conjugation and Shift Response
Chittasupho, Chuda Shannon, Laura Siahaan, Teruna J. Vines, Charlotte M. Berkland, Cory J.
Chittasupho, Chuda
Shannon, Laura
Siahaan, Teruna J.
Vines, Charlotte M.
Berkland, Cory J.
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Abstract
Dendritic cells (DCs) are potent professional antigen presenting cells (APC) that activate naïve T cells. Interaction of ICAM-1 and LFA-1 molecules on each cell is required for T cell conjugation to DCs which leads to naïve CD4+ T cell activation and proliferation. Nanoparticles capable of blocking LFA-1/ICAM-1 interaction were studied as inhibitors of T cell conjugation to DCs. Primary DCs were primed with ovalbumin, then treated with a peptide that binds ICAM-1 (LABL), a peptide that binds LFA-1 (cIBR) or the same peptides covalently linked to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles (NPs). LABL-NPs and cIBR-NPs rapidly bound to DCs and inhibited T cell conjugation to DCs to a greater extent than the free peptides, unconjugated nanoparticles (NPs), anti-ICAM-1 antibodies and anti-LFA-1 antibodies. In addition, DCs treated with NPs or with cIBR-NPs stimulated the proliferation of T cells, but DCs treated with LABL-NPs did not stimulate T cell proliferation. Nanoparticles targeting ICAM-1 or LFA-1 also altered cytokine production by DC cocultured with T cells when compared to free ligands suggesting these NPs may offer a unique tool for shaping T cell response.
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Date
2011-03-22
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ACS Nano
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Keywords
Peptides, Nanoparticles, Targeted delivery, Dendritic cells, T cell
Citation
Chittasupho, C., Shannon, L., Siahaan, T. J., Vines, C. M., & Berkland, C. (2011). Nanoparticles Targeting Dendritic Cell Surface Molecules Effectively Block T cell Conjugation and Shift Response. ACS Nano, 5(3), 1693–1702. http://doi.org/10.1021/nn102159g