title: In Vivo Enrichment of Diabetogenic T Cells.
abstract: Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and the rarity of autoimmune T cells in the blood hinder their study. We describe a method to enrich and harvest autoimmune T cells in vivo by using a biomaterial scaffold loaded with protein antigens. In model antigen systems, we found that antigen-specific T cells become enriched within scaffolds containing their cognate antigens. When scaffolds containing lysates from an insulin-producing β-cell line were implanted subcutaneously in autoimmune diabetes-prone NOD mice, β-cell-reactive T cells homed to these scaffolds and became enriched. These T cells induced diabetes after adoptive transfer, indicating their pathogenicity. Furthermore, T-cell receptor (TCR) sequencing identified many expanded TCRs within the β-cell scaffolds that were also expanded within the pancreata of NOD mice. These data demonstrate the utility of biomaterial scaffolds loaded with disease-specific antigens to identify and study rare, therapeutically important T cells.
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Thelin
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kissler
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Vigneault
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Watters
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.|School of Engineering and Applied Sciences, Harvard University, Cambridge, MA.
authors.forename: Des
authors.initials: D
authors.lastname: White
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.|School of Engineering and Applied Sciences, Harvard University, Cambridge, MA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA.
authors.forename: Sandeep T
authors.initials: ST
authors.lastname: Koshy
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Vermillion
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA.|School of Engineering and Applied Sciences, Harvard University, Cambridge, MA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA thomas.serwold@joslin.harvard.edu dr.omar.a.ali@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Serwold
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA thomas.serwold@joslin.harvard.edu dr.omar.a.ali@gmail.com.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Ali
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D015551:Autoimmunity / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D050417:Insulin-Secreting Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell