title: Characterization of specific immune responses to different Aspergillus antigens during the course of invasive Aspergillosis in hematologic patients.
abstract: Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1-3glucan, β1-3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA.
authors.affiliation: Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Policlinico, Modena, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Potenza
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallerini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Barozzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Riva
authors.forename: Fabio
authors.initials: F
authors.lastname: Forghieri
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.forename: Remi
authors.initials: R
authors.lastname: Beau
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Monica
authors.initials: M
authors.lastname: Morselli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zanetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Quadrelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Codeluppi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Livio
authors.initials: L
authors.lastname: Pagano
authors.forename: Morena
authors.initials: M
authors.lastname: Caira
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.forename: Monica
authors.initials: M
authors.lastname: Maccaferri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.forename: Uliano
authors.initials: U
authors.lastname: Morandi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tazzioli
authors.forename: Massimo
authors.initials: M
authors.lastname: Girardis
authors.forename: Mario
authors.initials: M
authors.lastname: Delia
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Longo
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Franco
authors.initials: F
authors.lastname: Narni
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Imovilli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Apolone
authors.forename: Agostinho
authors.initials: A
authors.lastname: Carvalho
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Latgè
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000276:immunology*; D001228:Aspergillosis / Q000097:blood*; D001230:Aspergillus / Q000276:immunology* / Q000502:physiology; D005260:Female; D006405:Hematology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D000946:Antigens, Fungal
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