期刊
JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 5, 页码 847-856出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit237
关键词
Aspergillus fumigatus; Crf1; catalase 1; T-cell; epitope; adoptive immunotherapy
资金
- Doelfonds Leukemie of the Bontius Stichting of the Leiden University Medical Center
- Schering-Plough
Invasive aspergillosis is a serious infectious complication after allogeneic stem cell transplantation. One of the strategies to improve the management of aspergillosis is the adoptive transfer of antigen-specific T cells, the success of which depends on the development of a broad repertoire of antigen-specific T cells. In this study, we identified CD4+ T cells specific for the Aspergillus proteins Crf1 and catalase 1 in 18 of 24 healthy donors by intracellular staining for interferon gamma and CD154. Crf1- and catalase 1-specific T cells were selected on the basis of CD137 expression and underwent single-cell expansion. Aspergillus-specific T-cell clones mainly exhibited a T-helper cell 1 phenotype and recognized a broad variety of T-cell epitopes. Five novel Crf1 epitopes, 2 previously described Crf1 epitopes, and 30 novel catalase 1 epitopes were identified. Ultimately, by using overlapping peptides of Aspergillus fumigatus proteins, Aspergillus-specific T-cell lines that have a broad specificity and favorable cytokine profile and are suitable for adoptive T-cell therapy can be generated in vitro.
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