Both central and peripheral tolerance mechanisms play roles in diabetes prevention in NOD-E transgenic mice

Richard J Mellanby, Jenny M Phillips, Nicole M Parish, Anne Cooke

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The non-obese diabetic (NOD) mouse spontaneously develops diabetes and is a widely used model of Type 1 Diabetes in humans. The major histocompatibility complex class II plays an important role in governing disease susceptibility in NOD mice. NOD mice express a rare I-A allele, I-A(g7), and do not express I-E molecules. Interestingly, transgenic NOD mice which express I-E (NOD-E) fail to develop diabetes although, the protective mechanism(s) are incompletely understood. Initially, we explored whether diabetes prevention was due to deletion of autoreactive T cells. Through adoptive transfer with depletion of CD25+ T cells, we demonstrated that autoreactive T cells were present in the periphery of NOD-E mice. Although, BDC2.5NOD T cells proliferated less in the pancreatic lymph nodes of NOD-E mice, we found that they transferred disease with a similar kinetic in NOD.scid and NOD-E.scid recipients suggesting that there was little difference in peripheral antigen presentation in NOD-E mice. We also found that there were no proportional or functional differences between NOD and NOD-E T regs. Our studies indicate that autoreactive T cells are present within the periphery of NOD-E mice but that these cells are present in low numbers suggesting that peripheral tolerogenic mechanisms are able to prevent them from inducing diabetes.
Original languageEnglish
Pages (from-to)383-394
Number of pages12
JournalAutoimmunity
Volume41
Issue number5
DOIs
Publication statusPublished - 2008

Keywords / Materials (for Non-textual outputs)

  • diabetes
  • NOD
  • NOD-E
  • central tolerance
  • Foxp3
  • CD25

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