title: Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis.
abstract: After allogeneic stem cell transplantation patients are at risk of invasive aspergillosis, especially during the period of neutropenia. Recent data suggest that impaired T-cell immune reconstitution after transplantation plays an important role in this increased risk. In this study we investigated whether Aspergillus-specific T cells are involved in the recovery from invasive aspergillosis by analyzing the Aspergillus-specific T-cell response in patients with invasive aspergillosis. In nine patients whose Aspergillus infection improved, we identified Crf1- or Catalase1-specific T cells on the basis of CD154 expression and interferon-γ production following stimulation with overlapping peptides of the A. fumigatus proteins Crf1 and Catalase1. These Aspergillus-specific T cells were induced at the moment of regression of the aspergillus lesions. Crf1- and Catalase1-specific T cells, sorted on the basis of CD154 expression at the peak of the immune response, had a T helper-1 phenotype and recognized a variety of T-cell epitopes. In contrast, in two patients with progressive invasive aspergillosis, no Crf1- or Catalase1-specific T cells were identified. These data indicate that the presence of Aspergillus-specific T cells with a T helper-1 phenotype correlates with the clearance of aspergillus infection.
authors.affiliation: Department of Hematology, Leiden University Medical Center Department of Infectious Diseases, Leiden University Medical Center.
authors.forename: Hetty
authors.initials: H
authors.lastname: Jolink
authors.affiliation: Department of Hematology, Leiden University Medical Center.
authors.forename: Renate S
authors.initials: RS
authors.lastname: Hagedoorn
authors.affiliation: Department Molecular Microbiology and Biotechnology, Institute of Biology, Leiden University.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Lagendijk
authors.affiliation: Department of Immunohematology and Blood transfusion, Leiden University Medical Center, the Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Department of Hematology, Leiden University Medical Center.
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.affiliation: Department of Hematology, Leiden University Medical Center mhmheemskerk@lumc.nl.
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000276:immunology; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016130:Immunophenotyping; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D015898:Tomography Scanners, X-Ray Computed; D014184:Transplantation, Homologous
chemical_list: D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte
references.citation: J Clin Microbiol. 2004 Mar;42(3):1142-8
references.pmid: 15004066
references.citation: Blood. 2011 Jul 28;118(4):1121-31
references.pmid: 21642594
references.citation: J Med Virol. 2010 Jul;82(7):1208-15
references.pmid: 20513086
references.citation: J Immunol. 2000 Jul 1;165(1):381-8
references.pmid: 10861075
references.citation: Blood. 2011 Jun 2;117(22):5881-91
references.pmid: 21441461
references.citation: PLoS One. 2010 Feb 17;5(2):e9036
references.pmid: 20174463
references.citation: Blood. 2003 Nov 15;102(10):3807-14
references.pmid: 12791648
references.citation: Clin Exp Immunol. 2005 Feb;139(2):257-67
references.pmid: 15654824
references.citation: Microbes Infect. 2002 Nov;4(13):1281-90
references.pmid: 12443892
references.citation: J Infect Dis. 2013 Sep 1;208(5):847-56
references.pmid: 23698813
references.citation: Clin Infect Dis. 2008 Jun 15;46(12):1813-21
references.pmid: 18462102
references.citation: Blood. 2005 Dec 15;106(13):4397-406
references.pmid: 16123217
references.citation: Clin Exp Immunol. 2008 Feb;151(2):284-96
references.pmid: 18005260
references.citation: J Infect Dis. 1999 Dec;180(6):1957-68
references.pmid: 10558953
references.citation: Blood. 2002 Dec 15;100(13):4521-8
references.pmid: 12393638
references.citation: Clin Infect Dis. 2007 Nov 1;45(9):1161-70
references.pmid: 17918077
references.citation: Immunology. 2010 May;130(1):46-54
references.pmid: 20002791
references.citation: Cytotherapy. 2004;6(3):223-34
references.pmid: 15203979
references.citation: J Immunol. 2009 Aug 15;183(4):2407-14
references.pmid: 19625642