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.