title: Multispecific Aspergillus T cells selected by CD137 or CD154 induce protective immune responses against the most relevant mold infections.
abstract: BACKGROUND
  Aspergillus and Mucorales species cause severe infections in patients after hematopoietic stem cell transplantation (HSCT). Induction of antifungal CD4(+) T-helper type 1 (Th1) immunity is an appealing strategy to combat these infections. Immunotherapeutic approaches are so far limited because of a lack of antigens inducing protective T cells, their elaborate production, and the need of targeting a broad spectrum of pathogenic fungi.
  
  
  METHODS
  We examined the response to different Aspergillus fumigatus proteins in healthy individuals and patients after HSCT and compared rapid selection protocols for fungus-specific T cells based on CD137 or CD154 expression.
  
  
  RESULTS
  The A. fumigatus proteins Crf1, Gel1, and Pmp20 induced strong Th1 responses in healthy individuals. T cells specific for these antigens expanded in patients with active invasive aspergillosis, indicating their contribution to infection control. Th1 cells specific for the 3 proteins can be selected with similar specificity within 24 hours, based on CD137 or CD154 expression. These cells recognize naturally processed A. fumigatus and the multispecific T-cell lines, directed against all 3 proteins, especially those selected by CD154, additionally cross-react to different Aspergillus and Mucorales species.
  
  
  CONCLUSIONS
  These findings may form the basis for adoptive T-cell transfer for prophylaxis or treatment in patients with these devastating infections.
authors.affiliation: Infection Biology Laboratory, Department of Biomedicine.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stuehler
authors.affiliation: Infection Biology Laboratory, Department of Biomedicine.
authors.forename: Justyna
authors.initials: J
authors.lastname: Nowakowska
authors.affiliation: Infection Biology Laboratory, Department of Biomedicine Division of Infectious Diseases and Hospital Epidemiology, Departments of Biomedicine and Clinical Research.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bernardini
authors.affiliation: Division of Hematology, Department of Internal Medicine II, University of Wuerzburg, Germany.
authors.forename: Max S
authors.initials: MS
authors.lastname: Topp
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, Departments of Biomedicine and Clinical Research.
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.affiliation: Division of Hematology, University Hospital of Basel, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.affiliation: Infection Biology Laboratory, Department of Biomedicine Division of Infectious Diseases and Hospital Epidemiology, Departments of Biomedicine and Clinical Research.
authors.forename: Nina
authors.initials: N
authors.lastname: Khanna
mesh_terms: D000328:Adult; D000946:Antigens, Fungal / Q000276:immunology*; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D005656:Fungal Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D023201:CD40 Ligand
keywords: Aspergillus; CD137 and CD154 expression; T-cell therapy; fungal infection; multispecific T cells