Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non‐deletional mechanism

Sandra D. Husbands, Gunther Schönrich, Bernd Arnold, Phillip R. Chandler, Elizabeth Simpson, Karen L. Philpott, Peter Tomlinson, Lorraine O'Reilly, Anne Cooke, Andrew L. Mellor

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Transgenic CBA (H‐2k haplotype) mice expressing the H‐2 Kb major histocompatibility complex (MHC) class I gene under control of transcriptional promoter elements from a milk protein gene display high‐level H‐2 Kb transcription in lactating mammary glands and low‐level transcription in skin and thymus of male and virgin female transgenic mice. However, H‐2 Kb antigen could be detected only in lactating mammary gland epithelial cells by immunohistological methods. All transgenic mice are tolerant of H‐2 Kb since they fail to reject skin grafts from mice expressing H‐2 Kb molecules. Furthermore, anti‐H‐2 Kb cytotoxic responses could not be generated using responder T cells from transgenic mice but T cells from the same mice proliferated, in the presence of interleukin‐2, in response to stimulator cells expressing H‐2 Kb. Tolerance to H‐2 Kb is induced in the thymus since CBA mice grafted with thymus tissue from transgenic mice fail to reject H‐2 Kb disparate skin grafts. However, experiments with double‐transgenic mice also expressing a T cell receptor with anti‐H‐2 Kb specificity reveal that tolerance induction is not brought about by elimination of thymocytes bearing H‐2 Kb‐reactive receptors. Instead, a non‐deletional mechanism which results in down‐modulation of both CD8 and T cell receptor expression in peripheral T cells correlates with the induction of tolerance in these mice. These data reveal that extremely low levels of self‐antigen expression in the thymus are sufficient to induce tolerance via non‐deletional mechanisms.

Original languageEnglish (US)
Pages (from-to)2655-2661
Number of pages7
JournalEuropean Journal of Immunology
Volume22
Issue number10
DOIs
StatePublished - Jan 1 1992

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Histocompatibility Antigens Class I
Major Histocompatibility Complex
Thymus Gland
Transgenic Mice
T-Lymphocytes
Human Mammary Glands
T-Cell Antigen Receptor
Skin
H-2 Antigens
MHC Class I Genes
Transplants
Inbred CBA Mouse
Histamine H2 Receptors
Milk Proteins
Thymocytes
Haplotypes
Epithelial Cells
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non‐deletional mechanism. / Husbands, Sandra D.; Schönrich, Gunther; Arnold, Bernd; Chandler, Phillip R.; Simpson, Elizabeth; Philpott, Karen L.; Tomlinson, Peter; O'Reilly, Lorraine; Cooke, Anne; Mellor, Andrew L.

In: European Journal of Immunology, Vol. 22, No. 10, 01.01.1992, p. 2655-2661.

Research output: Contribution to journalArticle

Husbands, SD, Schönrich, G, Arnold, B, Chandler, PR, Simpson, E, Philpott, KL, Tomlinson, P, O'Reilly, L, Cooke, A & Mellor, AL 1992, 'Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non‐deletional mechanism', European Journal of Immunology, vol. 22, no. 10, pp. 2655-2661. https://doi.org/10.1002/eji.1830221027
Husbands, Sandra D. ; Schönrich, Gunther ; Arnold, Bernd ; Chandler, Phillip R. ; Simpson, Elizabeth ; Philpott, Karen L. ; Tomlinson, Peter ; O'Reilly, Lorraine ; Cooke, Anne ; Mellor, Andrew L. / Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non‐deletional mechanism. In: European Journal of Immunology. 1992 ; Vol. 22, No. 10. pp. 2655-2661.
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