Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production.
Natural rubber latex (NRL; Hevea brasiliensis) allergy is an IgE-mediated reaction to latex proteins. When latex glove exposure is the main sensitizing agent, Hev b 5 is one of the major allergens. Dendritic cells (DC), the main antigen presenting cells, modulated with pharmacological agents can restore tolerance in several experimental models, including allergy. In the current study, we aimed to generate DC with tolerogenic properties from NRL-allergic patients and evaluate their ability to modulate allergen-specific T and B cell responses. Here we show that dexamethasone-treated DC (dxDC) differentiated into a subset of DC, characterized by low expression of MHC class II, CD40, CD80, CD86 and CD83 molecules. Compared with LPS-matured DC, dxDC secreted lower IL-12 and higher IL-10 after CD40L activation, and induced lower alloantigenic T cell proliferation. We also show that dxDC pulsed with the dominant Hev b 5 T-cell epitope peptide, Hev b 5(46-65), inhibited both proliferation of Hev b 5-specific T-cell lines and the production of Hev b 5-specific IgE. Additionally, dxDC induced a subpopulation of IL-10-producing regulatory T cells that suppressed proliferation of Hev b 5-primed T cells. In conclusion, dxDC generated from NRL-allergic patients can modulate allergen-specific T-cell responses and IgE production, supporting their potential use in allergen-specific immunotherapy.
Research Institute of Dental Science, Faculty of Dentistry, University of Chile, Santiago, Chile.
Alejandro
A
Escobar
Department of Pharmacy, Faculty of Chemistry, Catholic University of Chile, Santiago, Chile.
Adam
A
Aguirre
Allergy Center, Clinical Hospital of University of Chile, University of Chile, Santiago, Chile.
María Antonieta
MA
Guzmán
Blood bank Clinical Hospital of University of Chile, University of Chile, Santiago, Chile.
Rodrigo
R
González
Immunology Program, Faculty of Medicine, University of Chile Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Diego
D
Catalán
Department of Biology, Faculty of Chemistry and Biology, University of Santiago, Santiago, Chile.
Claudio
C
Acuña-Castillo
Blood bank Clinical Hospital of University of Chile, University of Chile, Santiago, Chile.
Milton
M
Larrondo
Immunology Program, Faculty of Medicine, University of Chile Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Mercedes
M
López
Immunology Program, Faculty of Medicine, University of Chile Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Barbara
B
Pesce
Department of Immunology, AMREP, Monash University, Melbourne, Australia.
Jennifer
J
Rolland
Department of Immunology, AMREP, Monash University, Melbourne, Australia.
Robyn
R
O'Hehir
Immunology Program, Faculty of Medicine, University of Chile Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
Juan Carlos
JC
Aguillón
D000328:Adult; D000485:Allergens / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D052179:Antigens, Plant / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020315:Latex Hypersensitivity / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D000485:Allergens; D015703:Antigens, CD; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D010940:Plant Proteins; C101800:allergen Hev b 5; D016753:Interleukin-10; D007073:Immunoglobulin E; D003907:Dexamethasone