title: B cells "transduced" with TAT-fusion proteins can induce tolerance and protect mice from diabetes and EAE.
abstract: Antigen-immunoglobulin fusion protein expressing B cells have been shown as excellent tolerogenic antigen-presenting cells in multiple disease models. Using efficient protein transduction by fusion with a HIV TAT protein transduction domain, we herein tested the TAT-fusion protein transduced B cells for their effects in antigen-specific tolerance induction in two animal models, experimental autoimmune encephalomyelitis (EAE) and type 1 diabetes. We demonstrated that transfer of TAT-MOG35-55 (myelin oligodendrocyte glycoprotein)-Ig 'transduced B cells' 10 days after EAE induction significantly protected mice from disease. Similarly, the onset of disease was delayed when NOD mice received insulin specific TAT-B9-23-B cells. Surprisingly, no protection against EAE was observed in a prophylactic protocol when transduced B cells were given before disease induction. Moreover, TAT-ovalbumin transduced cells were tolerogenic in primed but not naïve mice. Our results suggest that TAT-fusion protein transduced B cells were tolerogenic in antigen primed recipients, a condition clinically relevant to autoimmune diseases.
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Nana
authors.initials: N
authors.lastname: Owusu-Boaitey
authors.forename: Jonathan
authors.initials: J
authors.lastname: Skupsky
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D015696:Gene Products, tat / Q000276:immunology*; D007108:Immune Tolerance; D007328:Insulin / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*
chemical_list: D015696:Gene Products, tat; D007328:Insulin; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C097877:insulin B (9-23)