Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus
Author:
Olaf Beck, Max S. Topp, Ulrike Koehl, Emmanuel Roilides, Maria Simitsopoulou, Mitra Hanisch, Jacqueline Sarfati, Jean Paul LatgÉ, Thomas Klingebiel, Hermann Einsele, and Thomas Lehrnbecher
Date: 17 April 2006
Abstract:
Invasive aspergillosis remains a serious complication in patients undergoing allogeneic stem cell transplantation (SCT). Since it became clear that lymphocytes provide a critical secondary defense against fungi, adoptive transfer of functionally active anti-Aspergillus T cells might be an option to restore adaptive immune effector mechanisms. Using the interferon (IFN)-{gamma} secretion assay, we isolated human activated T cells upon stimulation with a cellular extract of Aspergillus fumigatus. Culturing this cell population for 14 days, we obtained an average of 1.1 x 107 cells from a single 100-mL blood draw in 7 of 7 healthy individuals. Within another 14 days, these cells were expanded to an average number of 2.0 x 108 T-helper 1 (TH1) cells secreting IFN-{gamma} on stimulation with Aspergillus antigens. Testing various fungal antigen extracts, similar proportions of IFN-{gamma}-producing CD3+/CD4+ cells were obtained upon activation with antigen extracts of A fumigatus, A flavus, A niger, and Penicillium chrysogenum, whereas no significant IFN-{gamma} production was observed upon activation with antigen extracts of Alternaria alternata and Candida albicans. In addition, generated T cells were able to induce damage to A fumigatus hyphae, and significantly increased hyphal damage induced by human neutrophils. CD4+ T-cell-mediated alloreactivity of generated anti-Aspergillus T cells was clearly reduced compared with that of the original cell population. In conclusion, we present a simple and feasible strategy for rapid generation of a high number of functional active T cells against Aspergillus from a single blood draw. Our data suggest that functionally active T cells against Aspergillus could be a promising treatment option for patients undergoing allogeneic SCT. (Blood. 2006;107: 2562-2569)
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