Characterization of CD8+ T lymphocytes that persist after peripheral tolerance to a self antigen expressed in the pancreas

J Immunol. 2000 Jan 1;164(1):191-200. doi: 10.4049/jimmunol.164.1.191.

Abstract

As a result of expression of the influenza hemagglutinin (HA) in the pancreatic islets, the repertoire of HA-specific CD8+ T lymphocytes in InsHA transgenic mice (D2 mice expressing the HA transgene under control of the rat insulin promoter) is comprised of cells that are less responsive to cognate Ag than are HA-specific CD8+ T lymphocytes from conventional mice. Previous studies of tolerance induction involving TCR transgenic T lymphocytes suggested that a variety of different mechanisms can reduce avidity for Ag, including altered cell surface expression of molecules involved in Ag recognition and a deficiency in signaling through the TCR complex. To determine which, if any, of these mechanisms pertain to CD8+ T lymphocytes within a conventional repertoire, HA-specific CD8+ T lymphocytes from B10.D2 mice and B10.D2 InsHA transgenic mice were compared with respect to expression of cell surface molecules, TCR gene utilization, binding of tetrameric KdHA complexes, lytic mechanisms, and diabetogenic potential. No evidence was found for reduced expression of TCR or CD8 by InsHA-derived CTL, nor was there evidence for a defect in triggering lytic activity. However, avidity differences between CD8+ clones correlated with their ability to bind KdHA tetramers. These results argue that most of the KdHA-specific T lymphocytes in InsHA mice are not intrinsically different from KdHA-specific T lymphocytes isolated from conventional animals. They simply express TCRs that are less avid in their binding to KdHA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / biosynthesis*
  • CD3 Complex / physiology
  • CD8 Antigens / biosynthesis
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Separation
  • Clone Cells
  • Cytotoxicity, Immunologic / genetics
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Epitopes, T-Lymphocyte / immunology
  • H-2 Antigens / immunology
  • H-2 Antigens / metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Immune Tolerance* / genetics
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Transgenic
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Species Specificity
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Autoantigens
  • CD3 Complex
  • CD8 Antigens
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Antigen, T-Cell