Exposure to sequestered self-antigens in vivo is not sufficient for the induction of autoimmune diabetes

Nobuyuki Ono, Kiichi Murakami, Olivia Chan, Håkan Hall, Alisha R. Elford, Patty Yen, Thomas Calzascia, David M. Spencer, Pamela S. Ohashi, Salim Dhanji

Research output: Contribution to journalArticle

Abstract

Although the role of T cells in autoimmunity has been explored for many years, the mechanisms leading to the initial priming of an autoimmune T cell response remain enigmatic. The 'hit and run' model suggests that self-antigens released upon cell death can provide the initial signal for a self-sustaining autoimmune response. Using a novel transgenic mouse model where we could induce the release of self-antigens via caspase-dependent apoptosis. We tracked the fate of CD8+ T cells specific for the self-antigen. Our studies demonstrated that antigens released from apoptotic cells were cross-presented by CD11c+ cells in the draining lymph node. This cross-presentation led to proliferation of self-antigen specific T cells, followed by a transient ability to produce IFN-ã, but did not lead to the development of autoimmune diabetes. Using this model we examined the consequences on T cell immunity when apoptosis was combined with dendritic cell maturation signals, an autoimmune susceptible genetic background, and the deletion of Tregs. The results of our study demonstrate that autoimmune diabetes cannot be initiated by the presentation of antigens released from apoptotic cells in vivo even in the presence of factors known to promote autoimmunity.

Original languageEnglish
Article numbere0173176
JournalPloS one
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Ono, N., Murakami, K., Chan, O., Hall, H., Elford, A. R., Yen, P., Calzascia, T., Spencer, D. M., Ohashi, P. S., & Dhanji, S. (2017). Exposure to sequestered self-antigens in vivo is not sufficient for the induction of autoimmune diabetes. PloS one, 12(3), [e0173176]. https://doi.org/10.1371/journal.pone.0173176