Mast cell degranulation breaks peripheral tolerance

Am J Transplant. 2009 Oct;9(10):2270-80. doi: 10.1111/j.1600-6143.2009.02755.x. Epub 2009 Jul 22.


Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Degranulation*
  • DNA Primers
  • Graft Rejection
  • Heart Transplantation / immunology
  • Immune Tolerance*
  • Inflammation Mediators / immunology
  • Mast Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Skin Transplantation / immunology
  • T-Lymphocytes / immunology
  • Transplantation, Homologous


  • DNA Primers
  • Inflammation Mediators