An HIV-1 tat-autoantigen fusion protein suppresses insulitis in NOD mice |
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Authors: | Tae-Geum Kim Jie Yu John Hough David Henderson William H R Langridge |
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Institution: | (1) Center for Molecular Biology and Gene Therapy, 161, Mortensen Hall, Department of Biochemistry & Microbiology, Loma Linda University, 92350 Loma Linda, CA;(2) Department of Anatomy, Loma Linda University, 92350 Loma Linda, CA |
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Abstract: | To assess the immunomodulatory activity of the HIV Tat transduction peptide for enhancement of suppression of Type 1 autoimmune
diabetes, the 11 amino acid HIV-1 Tat transduction peptide was genetically linked to the major islet autoantigens proinsulin
(INS) and glutamic acid decarboxylase (GAD). The Tat-autoantigen fusion proteins were synthesized in Escherichia coli and characterized by acrylamide gel separation and immunoblot analysis. Histological examination of pancreatic islets isolated
from juvenile NOD mice inoculated orally with the Tat-autoantigen conjugates revealed a significant reduction in islet inflammation
(insulitis) in comparison with islets from unimmunized mice. Increased serum IgG1 antibody isotype titers detected in Tat-autoantigen
inoculated mice suggest that the transduction peptide-autoantigen fusion proteins stimulate Th2 lymphocyte mediated bystander
suppression. The reduction of islet insulitis observed in Tat-autoantigen inoculated mice suggests that the adjuvant effect
of the Tat transduction peptide resides in Tat enhanced delivery of linked autoantigens through enterocytes to lymphocytes
in the gut-associated lymphoid tissues. |
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Keywords: | Autoimmune diabetes AIDS Tat transduction peptide insulin glutamic acid decarboxylase adjuvant NOD mouse |
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