Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells

Eur J Immunol. 1992 Apr;22(4):1013-22. doi: 10.1002/eji.1830220421.


To study the basis for immunological tolerance of peripheral tissue-specific antigens, a transgenic mouse line was established that expresses the influenza hemagglutinin (HA) on pancreatic islet beta cells (Ins-HA transgenic mice). When followed up to 14 months of age, Ins-HA transgenic mice did not develop spontaneous autoimmune disease. Upon immunization with HA-expressing viruses, high titers of HA-specific circulating antibody were detected; however, T cell responses by both the T helper and T cytolytic compartment were markedly reduced as compared with transgene-negative littermates, and no evidence could be found for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from transgene-negative mice plus virus into irradiated Ins-HA hosts resulted in islet inflammation dominated by CD4+ T cells, indicating that the HA antigen was accessible to activated T cells. These results suggest that T cells can be rendered tolerant of antigens expressed outside the thymus.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8 Antigens / analysis
  • Cytotoxicity, Immunologic
  • Hemagglutinins, Viral / immunology*
  • Immune Tolerance*
  • Immunization, Passive
  • Influenza A virus / immunology
  • Islets of Langerhans / immunology*
  • Lymphocyte Activation
  • Major Histocompatibility Complex
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Helper-Inducer / immunology


  • CD8 Antigens
  • Hemagglutinins, Viral
  • Peptides