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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.
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TRANSPLANTATION
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 Latgé,
Thomas Klingebiel,
Hermann Einsele, and
Thomas Lehrnbecher
From the Pediatric Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany; Medizinische Poliklinik, Julius-Maximilians University, Würzburg, Germany; 3rd Department of Pediatrics, University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece; and Institut Pasteur, Paris, France.
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 1.1 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- 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 Penicillium chrysogenum, whereas no significant IFN- 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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