Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus

被引:98
作者
Beck, O
Topp, MS
Koehl, U
Roilides, E
Simitsopoulou, M
Hanisch, M
Sarfati, J
Latgé, JP
Klingebiel, T
Einsele, H
Lehrnbecher, T
机构
[1] Goethe Univ Frankfurt, D-6000 Frankfurt, Germany
[2] Univ Wurzburg, Med Poliklin, D-8700 Wurzburg, Germany
[3] Univ Thessaloniki, Dept Pediat 3, Hippokrat Hosp, Thessaloniki, Greece
[4] Inst Pasteur, Paris, France
关键词
D O I
10.1182/blood-2005-04-1660
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 10(7) 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 10(8) T-helper 1 (THII) 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 Aspergilius 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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收藏
页码:2562 / 2569
页数:8
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