The role of alum-induced host DNA release in antigen-presenting cell activation and T cell priming
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1
University of Colorado Anschutz Medical Campus, Immunology, United States
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2
National Jewish Health, Immunology, United States
Aluminum salts (alum) are widely used as adjuvants in human vaccines even though their mechanism of action remains unclear. It is known that host DNA rapidly coats injected alum and may be responsible for immune cell stimulation. Intramuscular immunization with alum plus influenza A nucleoprotein stimulates robust CD4+ T cell responses. We have confirmed that this response is attenuated if DNAse is co-injected with alum and nucleoprotein. Our experiments suggest that host DNA, induced by alum, increases the interaction time between antigen specific T cells and antigen presenting cells (APCs). Following alum immunization, at least three distinct populations of antigen-loaded cells appear in the draining lymph nodes: monocytes, migratory dendritic cells, and B cells. We therefore hypothesize that host DNA, released upon immunization with alum, contributes to alum’s adjuvanticity by activating one or more of these sets of APCs. DNAse treatment does not prevent any of these cell populations from taking up antigen or migrating to draining lymph nodes, but it may alter the stimulatory qualities of these cells. Therefore, we are currently assessing how DNAse co-injection alters the activation profiles of antigen-loaded APCs and their ability to prime CD4+ T cells. We expect that one or more subsets of APCs depend on host DNA stimulus to effectively prime T cells upon alum immunization. These studies contribute to our understanding of the role of host DNA release in alum’s adjuvant effect.
Keywords:
Antigen-Presenting Cells,
CD4-Positive T-Lymphocytes,
Adjuvants, Immunologic,
DNA,
T cell priming
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Noges
L,
McKee
A,
Kappler
J and
Marrack
P
(2013). The role of alum-induced host DNA release in antigen-presenting cell activation and T cell priming.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00114
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Received:
09 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Laura Noges, University of Colorado Anschutz Medical Campus, Immunology, Aurora, United States, laura.noges@ucdenver.edu