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. 1989 Nov;84(5):1550–1554. doi: 10.1172/JCI114331

Tolerance induced by physiological levels of secreted proteins in transgenic mice expressing human insulin.

P J Whiteley 1, J P Lake 1, R F Selden 1, J A Kapp 1
PMCID: PMC304020  PMID: 2681269

Abstract

We have used transgenic mice to study immune tolerance to autologous, non-MHC encoded proteins that are expressed at physiological levels in the circulation. The transgenic mice used in these studies express the human preproinsulin gene and synthesize human proinsulin. Human and mouse insulin are secreted from the pancreatic islets of transgenic mice in response to normal physiological stimuli, such as glucose. Our data demonstrate that the transgenic mice have acquired tolerance to human insulin. The repertoire of T cells specific for exogenous antigens is shaped by the acquired tolerance to autologous proteins since pork but not beef or sheep insulin is also nonimmunogenic in the transgenic mice. We also found that the transgenic mice were tolerant to human proinsulin, the intracellular precursor of insulin. Unresponsiveness to human proinsulin most likely results from tolerance of insulin-specific and proinsulin-specific T cells that recognize the secreted enzymatic cleavage products of proinsulin, insulin and C-peptide.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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