T cell-mediated beta cell destruction: Autoimmunity and alloimmunity in the context of type 1 diabetes

Adam L. Burrack, Tijana Martinov, Brian T Fife

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications. Ideally a successful approach would target only the destructive immune cells and leave the remaining immune system intact to fight foreign pathogens. This review discusses the autoimmune diabetes disease process, diabetic complications that warrant a transplant, and alloimmunity. First, we describe the current understanding of autoimmune destruction of beta cells including the roles of CD4 and CD8 T cells and several possibilities for antigen-specific tolerance induction. Second, we outline diabetic complications necessitating beta cell replacement. Third, we discuss transplant recognition, potential sources for beta cell replacement, and tolerance-promoting therapies under development. We hypothesize that a better understanding of autoreactive T cell targets during disease pathogenesis and alloimmunity following transplant destruction could enhance attempts to re-establish tolerance to beta cells.

Original languageEnglish (US)
Article number343
JournalFrontiers in Endocrinology
Issue numberDEC
StatePublished - Dec 5 2017

Bibliographical note

Funding Information:
BF is supported by NIH R01 AI106791, P01 AI35296, U24 AI118635, and Regenerative Medicine of Minnesota RMM #11215 TR002. AB is supported by NIH T32DK007203. TM is supported by the Frieda Martha Kunze Fellowship.

Publisher Copyright:
© 2017 Burrack, Martinov and Fife.


  • Alloimmunity
  • Autoimmune diseases
  • Immunology
  • T cells
  • Tolerance induction
  • Transplantation immunology
  • Type 1 diabetes


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