Journal
CLINICAL IMMUNOLOGY
Volume 160, Issue 1, Pages 103-123Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.03.004
Keywords
Tolerogenic; Microspheres; Diabetes; Dendritic; Immunotherapy; Antigen
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Funding
- Juvenile Diabetes Research Foundation [17-2007-1066, 17-2012-348]
- NIH NIDDK [DK063499]
- NIH NIAID [AI81218]
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We have developed novel antisense oligonucleotide-formulated microspheres that can reverse hyperglycemia in newly-onset diabetic mice. Dendritic cells taking up the microspheres adopt a restrained co-stimulation ability and migrate to the pancreatic lymph nodes when injected into an abdominal region that is drained by those lymph nodes. Furthermore, we demonstrate that the absolute numbers of antigen-specific Foxp3+ T regulatory cells are increased only in the lymph nodes draining the site of administration and that these T-cells proliferate independently of antigen supply in the microspheres. Taken together, our data add to the emerging model where antigen supply may not be a requirement in vaccines for autoimmune disease, but the site of administration - subserved by lymph nodes draining the target organ - is in fact critical to foster the generation of antigen-specific regulatory cells. The implications of these observations on vaccine design for autoimmunity are discussed and summarized. (C) 2015 Elsevier Inc. All rights reserved.
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