title: Elimination of T cell reactivity to pancreatic β cells and partial preservation of β cell activity by peptide blockade of LFA-1:ICAM-1 interaction in the NOD mouse model.
abstract: In insulin dependent diabetes mellitus (T1D), self-reactive T cells infiltrate pancreatic islets and induce beta cell destruction and dysregulation of blood glucose. A goal is to control only the self-reactive T cells, leaving the remainder of the T cell population free to protect the host. One approach is blockade of the second signal for T cell activation while allowing the first (antigen-specific) signal to occur. This work proposes that small peptides that block interaction of second signals delivered through the counter receptors LFA-1:ICAM-1 will induce attacking T cells (receiving the antigen signal) to become anergic or undergo apoptosis. In NOD mice, the peptides eliminated T cell reactivity against pancreatic antigens and reduced cellular infiltration into islets, which retained stronger density of insulin staining at five weeks after cessation of therapy. In in vitro studies the peptides induced nonresponsiveness during activation of T cells from mice and from human peripheral blood.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Abby L
authors.initials: AL
authors.lastname: Dotson
authors.forename: Lesya
authors.initials: L
authors.lastname: Novikova
authors.forename: Lisa
authors.initials: L
authors.lastname: Stehno-Bittel
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Benedict
mesh_terms: D000375:Aging; D000818:Animals; D001786:Blood Glucose; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D016169:Lymphocyte Function-Associated Antigen-1; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1
keywords: Autoimmunity; Diabetes; ICAM-1:LFA-1; NOD mice; Peptide costimulatory blockade; T cell tolerance