title: Sensitizing and Th2 adjuvant activity of cysteine protease allergens.
abstract: BACKGROUND
  Innate properties that enhance immune responses might increase the propensity of certain allergens to induce allergic sensitization. Either a direct adjuvant effect or the increased immune response to the allergen could then increase allergic responses to bystander antigens. Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa.
  
  
  METHODS
  Animals were sensitized with either enzymatically active, inactive or non-activated cysteine proteases via the nasal mucosa. Following two sensitization phases, mice were challenged with a higher dose of allergen. For bystander sensitization, mice received recombinant Der p 2 at sensitization in conjunction with the cysteine protease and were challenged with rDer p 2 alone. Sensitization was determined by measuring allergen-specific antibody responses and cytokine and cellular infiltrates into the lungs following challenge.
  
  
  RESULTS
  Sensitization for Th2-type lung hypersensitivity for both the cysteine protease and bystander antigens was readily achieved and both were dependent on the proteolytic activity of the allergen. Bystander adjuvant activity was demonstrated for mice that were low IgE responders to the cysteine protease, showing a response independent from the immune response to the enhancing cysteine protease. Airway hyperreactivity was induced in the susceptible NOD strain of mouse, and mice subjected to prolonged administration of papain maintained the ability to produce lung hypersensitivity and Th2-type responses.
  
  
  CONCLUSIONS
  These experiments demonstrate that cysteine protease activity at low doses can be an adjuvant for respiratory Th2 responses for themselves and bystander antigens in the absence of another adjuvant.
authors.affiliation: Centre for Child Health Research, University of Western Australia, Subiaco, W.A., Australia. paulac@ichr.uwa.edu.au
authors.forename: Paula T
authors.initials: PT
authors.lastname: Cunningham
authors.forename: Claire E
authors.initials: CE
authors.lastname: Elliot
authors.forename: Jason C
authors.initials: JC
authors.lastname: Lenzo
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Jarnicki
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Larcombe
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Thomas
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D001249:Asthma / Q000276:immunology; D057056:Cysteine Proteases / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D051381:Rats; D017207:Rats, Sprague-Dawley; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D007073:Immunoglobulin E; D057056:Cysteine Proteases