title: Mast cell degranulation breaks peripheral tolerance.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: de Vries
authors.forename: A
authors.initials: A
authors.lastname: Wasiuk
authors.forename: K A
authors.initials: KA
authors.lastname: Bennett
authors.forename: M J
authors.initials: MJ
authors.lastname: Benson
authors.forename: R
authors.initials: R
authors.lastname: Elgueta
authors.forename: T J
authors.initials: TJ
authors.lastname: Waldschmidt
authors.forename: R J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D000818:Animals; D001483:Base Sequence; D015550:Cell Degranulation; D017931:DNA Primers; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000276:immunology; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators
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