Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promoters

A. M. Sponaas, P. D. Tomlinson, J. Antoniou, N. Auphan, C. Langlet, B. Malissen, A. M. Schmitt-Verhulst, A. L. Mellor

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Abstract

We have studied tolerance onduction in transgenic CBA mice expressing H-2Kb genes under the influence of guinea-pig α-lactalbumln (KAL) or human β-globln gene promoter (Kβ). KAL radlo-reslstant cells, but not bone marrow derived cells, Induce tolerance to H-2Kb In chlmerlc mice. In contrast, bone marrow derived and radio-resistant cells of Kβ mice induce tolerance. Although appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and Kβ mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In addition, dendritic cells and macrophages express H-2Kb molecules when Kβ, but not when KAL bone marrow Is cultured in vitro. The mode of tolerance induction was examined in double transgenic mice by mating KAL or Kβ mice to mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8-independent cytotoxlc T cell clone. In both cases, a large number of Tg-TCR+ CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fall to appear suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and CD8-CD4- Tg-TCR+ T cells develop in double transgenic mice and respond to activation through their TCR - CD3 complex in vitro, although no responses to stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction in KAL and Kβ mice proceeds via a deletlonal mechanism that is inefficient due either to low numbers of H-2Kb expressing thymic cells or to the low levels of H-2Kb expressed by thymlc cells, or to a combination of these factors.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalInternational Immunology
Volume6
Issue number2
DOIs
StatePublished - Feb 1 1994

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Keywords

  • T cells
  • Tolerance
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sponaas, A. M., Tomlinson, P. D., Antoniou, J., Auphan, N., Langlet, C., Malissen, B., Schmitt-Verhulst, A. M., & Mellor, A. L. (1994). Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promoters. International Immunology, 6(2), 277-287. https://doi.org/10.1093/intimm/6.2.277