CD28 costimulation is critical for experimental allergic asthma in HLA-DQ8 transgenic mice.
The objective of this study was to investigate the contribution of the CD28 costimulatory molecules to allergen-induced primary and chronic inflammatory responses. To this end, we have developed and characterized a short ragweed allergen-induced asthma model involving sensitization of HLA-DQ transgenic mice followed by intranasal challenge with allergen. Forty-eight hours after primary challenge, sensitized DQ8 mice developed pulmonary eosinophilic inflammation, airway hyperreactivity, Th2 cytokines, and IgE/IgG1 Ab. This allergic inflammatory response was absent in H-2Abeta(0) and DQ8/CD28(0) mice. Secondary rechallenge with allergen 4 weeks later induced even greater inflammatory changes in the airways of DQ8 mice with eosinophils being the predominant inflammatory cells while only pulmonary lymphocytosis was observed in DQ8/CD28(0) mice. No inflammation was detected in H-2Abeta(0) mice. Proliferation and cytokine profile studies demonstrated that CD28 regulates T-cell activation and effector function. Therefore, CD28 is essential for the extrinsic asthma and can be a target for immunotherapy.
Chapoval
Svetlana P
SP
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
David
Chella S
CS
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity; D031164:Ambrosia; D000818:Animals; D001249:Asthma / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D007117:Immunization, Secondary; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D008218:Lymphocytosis / Q000209:etiology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity; D013047:Specific Pathogen-Free Organisms
D000485:Allergens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; D006183:H-2 Antigens; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D064532:Histocompatibility Antigen H-2D; D010936:Plant Extracts