The costimulatory molecules CD80, CD86 and OX40L are up-regulated in Aspergillus fumigatus sensitized mice.
Aspergillus fumigatus (Af) is a fungus associated with allergic bronchopulmonary aspergillosis (ABPA) and other allergic diseases. Immune responses in these diseases are due to T and B cell responses. T cell activation requires both Af-specific engagement of the T-cell-receptor as well as interaction of antigen independent costimulatory molecules including CD28-CD80/CD86 and OX40-OX40L interactions. Since these molecules and their interactions have been suggested to have a potential involvement in the pathogenesis of ABPA, we have investigated their role in a model of experimental allergic aspergillosis. BALB/c mice were primed and sensitized with Af allergens, with or without exogenous IL-4. Results showed up-regulation of both CD86 and CD80 molecules on lung B cells from Af-sensitized mice (79% CD86+ and 24% CD80+) and Af/rIL-4-treated mice (90% CD86+ and 24% CD80+) compared to normal controls (36% and 17%, respectively). Lung macrophages in Af-sensitized mice treated or not with IL-4 showed enhanced expression of these molecules. OX40L expression was also up-regulated on lung B cells and macrophages from both Af-sensitized and Af/rIL-4 exposed mice as compared to normal controls. All Af-sensitized animals showed peripheral blood eosinophilia, enhanced total serum IgE and allergen-specific IgG1 antibodies and characteristic lung inflammation. The up-regulation of CD80, CD86 and OX40L molecules on lung B cells and macrophages from Af-allergen exposed mice suggests a major role for these molecules in the amplification and persistence of immunological and inflammatory responses in ABPA.
Barrios
C S
CS
Allergy-Immunology Division, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, 53295, USA.
Johnson
B D
BD
D Henderson
J
J
Fink
J N
JN
Kelly
K J
KJ
Kurup
V P
VP
D000485:Allergens / Q000276:immunology; D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand; D013154:Spleen / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
D000485:Allergens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D015847:Interleukin-4; D007073:Immunoglobulin E