An HIV-1 tat-autoantigen fusion protein suppresses insulitis in NOD mice.
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.
Center for Molecular Biology and Gene Therapy, Department of Biochemistry & Microbiology Loma Linda University, CA 92350, USA.
Tae-Geum
TG
Kim
Jie
J
Yu
John
J
Hough
David
D
Henderson
William H R
WH
Langridge
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D054322:tat Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D001324:Autoantigens; D015696:Gene Products, tat; D007328:Insulin; D007527:Isoenzymes; D008024:Ligands; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2