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Novel Immunogens of Cellular Immunity Revealed using in vitro Human Cell-Based Approach
Title
Novel Immunogens of Cellular Immunity Revealed using in vitro Human Cell-Based Approach.
Creator
Schanen, Brian, Self, William, Warren, William, Khaled, Annette, Seal, Sudipta, Zervos, Antonis, University of Central Florida
Abstract / Description
Nanotechnology has undergone rapid expansion largely as a result of its enormous potential for applications as biomaterials, drug delivery vehicles, cancer therapeutics, and immunopotentiators. Despite this wave of interest and broad appeal for nanoparticles, evidence of their effect to the human immune system remains scarce. Concerns rise as studies on nanoparticle toxicology continue to emerge indicating that nanomaterials can be acutely toxic and can have long term inflammatory effects as...
Show moreNanotechnology has undergone rapid expansion largely as a result of its enormous potential for applications as biomaterials, drug delivery vehicles, cancer therapeutics, and immunopotentiators. Despite this wave of interest and broad appeal for nanoparticles, evidence of their effect to the human immune system remains scarce. Concerns rise as studies on nanoparticle toxicology continue to emerge indicating that nanomaterials can be acutely toxic and can have long term inflammatory effects as seen in animal models. Based on these findings and the rise in the development of nanoparticle technologies targeting in vivo applications, the urgency to characterize nanomaterial immunogenicity is paramount.Nanoparticles harbor great potential because they possess unique physicochemical properties compared to their larger counter parts as a result of quantum-size effects and their inherent large surface area to volume ratio. These physicochemical properties govern how a nanoparticle will behave in its environment. However, researchers have only just begun to catalogue the biological effect these properties illicit. We took it upon ourselves to investigate nanoparticle size-induced effects using TiO2, one of the most widely manufactured nanoparticles, as a model. We studied these effects in dendritic cells across a human donor pool. We examined dendritic cells because they have an inimitable functional role bridging the innate and adaptive arms of immunity. From this work we found that TiO2 nanoparticles can activate human dendritic cells to become pro-inflammatory in a size-dependent manner as compared to its micron-sized counterpart, revealing novel immune cell recognition and activation by a crystalline nanomaterial.Having identified nanomaterial size as a contributing feature of nanoparticle induced immunopotentiation, we became interested if additional physicochemical properties such as surface reactivity or catalytic behavior could also be immunostimulatory. Moreover, because we witnessed a stimulatory effect to dendritic cells following nanoparticle treatment, we were curious how these nanoparticle-touched dendritic cells would impact adaptive immunity. Since TiO2 acts as an oxidant we chose an antioxidant nanoparticle, CeO2, as a counterpart to explore how divergent nanoparticle surface reactivity impacts innate and adaptive immunity. We focused on the effect these nanoparticles had on human dendritic cells and TH cells as a strategy towards defining their impact to cellular immunity. Combined, we report that TiO2 nanoparticles potentiate DC maturation inducing the secretion of IL-12p70 and IL-1?, while treatment with CeO2 nanoparticles induced IL-10, a hallmark of suppression. When delivered to T cells alone TiO2 nanoparticles induced stronger proliferation in comparison to CeO2 which stimulated TReg differentiation. When co-cultured in allogeneic T cell assays, the materials directed alternate TH polarization whereby TiO2 drives largely a TH1 dominate response, whereas CeO2 was largely TH2 bias. Combined, we report a novel immunomodulatory capacity of nanomaterials with catalytic activity. While unintentional exposure to these nanomaterials could pose a serious health risk, development and targeted use of such immunomodulatory nanoparticles could provide researchers with new tools for novel adjuvant strategies or therapeutics.
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Date Issued
2012
Identifier
CFE0004629, ucf:49927
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004629