Healthy Human T-Cell Responses to Aspergillus fumigatus Antigens

• Published in: PloS one Vol. 5; no. 2; p. e9036
• Main Authors: Chaudhary, Neelkamal, Staab, Janet F., Marr, Kieren A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.02.2010; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Allergens; Allergies; Allergy; Antigens; Antigens, Fungal - genetics; Antigens, Fungal - immunology; Antigens, Fungal - isolation & purification; Aspergillus fumigatus; Aspergillus fumigatus - genetics; Aspergillus fumigatus - immunology; Aspergillus nidulans; Atopy; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell walls; Cells, Cultured; Cloning; Cystic fibrosis; Cytomegalovirus; E coli; Enzyme-Linked Immunosorbent Assay; Enzymes; Fungal Proteins - genetics; Fungal Proteins - immunology; Fungal Proteins - isolation & purification; Genes; Germination; Helper cells; Human behavior; Humans; Hyphae; Hyphae - genetics; Hyphae - immunology; Immunity; Immunology/Immunity to Infections; Infectious Diseases; Infectious Diseases/Fungal Infections; Infectious Diseases/Respiratory Infections; Inflammation; Interferon; Interferon-gamma - metabolism; Interleukin 17; Interleukin 4; Interleukin-17 - metabolism; Interleukin-4 - metabolism; Kinases; Laboratories; Ligands; Lung diseases; Lymphocytes; Lymphocytes T; Membrane proteins; Middle Aged; Morphology; Peptidylprolyl isomerase; Phosphopyruvate hydratase; Proteins; Recombinant Proteins - immunology; Recombinant Proteins - isolation & purification; Respiratory tract; Respiratory tract diseases; Spots; Stem cells; T cell receptors; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; γ-Interferon; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009036

Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H)1-T(H)17) and destructive allergic (T(H)2) immunity. How Aspergillus allergens (Asp f proteins) participate in the development of allergic sensitization is unknown. To determine whether Asp f proteins are strictly associated with T(H)2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17) to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H)1-responses to Asp f3 (a putative peroxismal membrane protein), Asp f9/16 (cell wall glucanase), Asp f11 (cyclophilin type peptidyl-prolyl isomerase) and Asp f22 (enolase). Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals. Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.