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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2562-2569.
Prepublished online as a Blood First Edition Paper on December 1, 2005; DOI 10.1182/blood-2005-04-1660.
 Previous Article | Next Article 
Submitted April 25, 2005
Accepted October 24, 2005
Generation of highly-purified and functionally active human TH1-cells against aspergillus fumigatus
Olaf Beck, Max S Topp, Ulrike Koehl, Emmanuel Roilides, Maria Simitsopoulou, Mitra Hanisch, Jacqueline Sarfati, Jean Paul Latge, Thomas Klingebiel, Hermann Einsele, and Thomas Lehrnbecher*
Pediatric Hematology and Oncology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt, Germany
Medizinische Poliklinik, Julius-Maximilians University, Wuerzburg, Germany
3rd Department of Pediatrics, University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
Institut Pasteur, Paris, France
* Corresponding author; email: Thomas.Lehrnbecher{at}kgu.de.
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)- 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 1.1x107 cells from a single 100-mL blood draw in 7 out of 7 healthy individuals. Within another 14 days, these cells were expanded to an average number of 2.0x108 TH1-cells secreting IFN- on stimulation with Aspergillus-antigens. Testing various fungal antigen extracts, similar proportions of IFN- producing CD3+/CD4+ cells were obtained upon activation with antigen extracts of A.fumigatus, A.flavus, A.niger and P. chrysogenum, whereas no significant IFN- production was observed upon activation with antigen extracts of A. alternata and C. 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.
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