Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies

Clin Immunol. 2010 Feb;134(2):121-9. doi: 10.1016/j.clim.2009.09.005.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • CD3 Complex / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / immunology*
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Muromonab-CD3 / therapeutic use*
  • Oligopeptides / immunology
  • Phenotype

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CD3 Complex
  • Histocompatibility Antigens Class I
  • Muromonab-CD3
  • Oligopeptides
  • teplizumab