MASTering the immune response: Mast cells in autoimmunity

Greg D. Gregory, Allison Bickford, Michaela Robbie-Ryan, Mindy Tanzola, Melissa A. Brown

Research output: Chapter in Book/Report/Conference proceedingConference contribution

13 Scopus citations

Abstract

Mast cells are established participants in allergic disease and in protection against extracellular parasites. Recently, it has become apparent that mast cells exert many profound effects on a variety of both innate and adaptive immune responses. Using mast cell-deficient WBB6F1/J-kit W/kitWv (W/Wv) mice, we have demonstrated that mast cells are critical for severe disease in a murine model of multiple sclerosis, experimental allergic encephalomyelitis (EAE). Reconstitution of the mast cell population in the periphery, but not the CNS, restores EAE severity. Mast cells exert their effects at both the inductive and effector phases of disease. EAE is mediated by autoreactive T cells that enter the CNS and initiate inflammatory responses, leading to demyelination within the spinal cord and brain. Although there are no intrinsic defects in W/Wv-derived T cells, both CD4+ and CD8+ autoreactive T cell responses are attenuated during early disease in W/Wv mice. Thus mast cells are essential for the optimal priming of autoreactive T cells. The entry of encephalitogenic T cells into the CNS is compromised in these mice as well. The effects on early T cell responses are due, in part, to the reduced percentage of activated dendritic cells in the lymph nodes of W/Wv mice after disease induction compared with wild-type mice. The finding that mast cells can alter T cell responses in EAE has much broader implications for understanding the impact of these cells on all T cell-mediated responses.

Original languageEnglish (US)
Title of host publicationMast Cells and Basophils
Subtitle of host publicationDevelopment, Activation and Roles in Allergic/Autoimmune Disease
Pages215-225
Number of pages11
StatePublished - Dec 1 2005

Publication series

NameNovartis Foundation Symposium
Volume271
ISSN (Print)1528-2511

ASJC Scopus subject areas

  • Medicine(all)

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