title: Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies.
abstract: The way in which anti-CD3 monoclonal antibodies (mAbs) modify human immune responses in type 1 diabetes (T1DM) is not known. We prepared a panel of Class I HLA-A2.1 tetramers with peptides from diabetes-associated antigens and studied the frequency and phenotype of the cells in patients with T1DM and blood donors and in patients treated with anti-CD3 mAb (Teplizumab). More patients with T1DM showed positive staining for at least 1 tetramer using frozen and fresh samples (p<0.05). Three months following treatment with anti-CD3 mAb, the proportion of GAD65- and InsB-peptide reactive CD8+ T cells increased (p<0.05). The phenotype of these cells was modulated from naïve to effector memoryRA+. We concludethat Class I MHC tetramers can identify antigen specific CD8+ T cells in patients with T1DM. The frequency of certain specificities increases after treatment with anti-CD3 mAb. Their modulated phenotype may have functional consequences for their pathogenicity.
authors.affiliation: Department of Immunobiology, Yale University, 10 Amistad Street, 131D, New Haven, CT 06520, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Cernea
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D009842:Oligopeptides / Q000276:immunology; D010641:Phenotype
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D016853:Muromonab-CD3; D009842:Oligopeptides; C502540:teplizumab