The efficacy of immunotherapy in an experimental murine model of allergic asthma is related to the strength and site of T cell activation during immunotherapy.
In the present study, the relation between the efficacy of immunotherapy, and the strength and site of T cell activation during immunotherapy was evaluated. We used a model of allergic asthma in which OVA-sensitized and OVA-challenged mice display increased airway hyperresponsiveness, airway inflammation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administration, or treatment with entire OVA or the immunodominant T cell epitope OVA(323-339), or treatment with a peptide analogue of OVA(323-339) with altered T cell activation capacity were studied. To gain more insight in how immunotherapy affects allergen-specific T cells, the site of Ag-specific T cell activation and the magnitude of the T cell response induced during different immunotherapy strategies were determined using an adoptive transfer model. Our data suggest that amelioration of airway hyperresponsiveness and inflammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 response. In contrast, deterioration of the disease after immunotherapy is associated with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.
Janssen
E M
EM
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
van Oosterhout
A J
AJ
Nijkamp
F P
FP
van Eden
W
W
Wauben
M H
MH
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D016056:Immunodominant Epitopes / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D000485:Allergens; D016056:Immunodominant Epitopes; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin