title: Recovery from desensitization of IgE-dependent responses in human lung mast cells.
abstract: BACKGROUND
  Clinical desensitization and oral food immunotherapy are therapeutic interventions that allow individuals who react adversely to an allergen (drug or food) to be made tolerant to the allergen. However, tolerance is brief, and allergen hypersensitivity can recur within days following allergen withdrawal.
  
  
  OBJECTIVE
  We hypothesize that the reason these treatments are temporary reflects rapid recovery of mast cells from a desensitized state. We sought to test this.
  
  
  METHODS
  Desensitization of IgE-mediated histamine release from human lung mast cells was explored by methods that partially replicate the pattern of treatment during clinical desensitization. Specific and non-specific desensitization and changes in surface IgE were examined following desensitization. Recovery from desensitization was also studied.
  
  
  RESULTS
  Desensitization of mast cell responses was readily induced with concentrations of antigen or anti-IgE that were suboptimal for secretion. There was little or no non-specific desensitization when lung mast cells were exposed to antigens. There was no loss of cell surface IgE following desensitization. Removing the desensitizing stimulus from the media following desensitization allowed the cells to recover with half-point of recovery of ~1.5 days and complete recovery after 5 days. Both the functional response and histamine content recovered within this time frame. The recovery appeared possible because both antigens and anti-IgE dissociated rapidly from cells after washing to remove excess stimulus.
  
  
  CONCLUSIONS
  Human lung mast cells readily recover from a desensitized state following removal of desensitizing antigen. This finding provides a potential explanation for the ephemeral nature of clinical desensitization.
authors.affiliation: Academic Unit of Respiratory Medicine, University of Sheffield, The Medical School, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: MacGlashan
authors.affiliation: Department of Histopathology, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Suvarna
authors.affiliation: Academic Unit of Respiratory Medicine, University of Sheffield, The Medical School, Sheffield, UK.
authors.forename: P T
authors.identifier: http://orcid.org/0000-0001-7272-3011
authors.initials: PT
authors.lastname: Peachell
mesh_terms: D003888:Desensitization, Immunologic; D005260:Female; D006632:Histamine / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D007073:Immunoglobulin E; D006632:Histamine
keywords: IgE; anti-IgE; antigen; desensitization; histamine; human lung mast cell