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Multispecific Aspergillus T Cells Selected by CD137 or CD154 Induce Protective Immune Responses Against the Most Relevant Mold Infections

Stuehler, Claudia ; Nowakowska, Justyna ; Bernardini, Claudia ; Topp, Max S. ; Battegay, Manuel ; Passweg, Jakob ; Khanna, Nina

In: The Journal of Infectious Diseases, 2015, vol. 211, no. 8, p. 1251-1261

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    Titre
    • Multispecific Aspergillus T Cells Selected by CD137 or CD154 Induce Protective Immune Responses Against the Most Relevant Mold Infections
    Auteur
    • Stuehler, Claudia. Infection Biology Laboratory, Department of Biomedicine
    • Nowakowska, Justyna. Infection Biology Laboratory, Department of Biomedicine
    • Bernardini, Claudia. Infection Biology Laboratory, Department of Biomedicine
    • Topp, Max S.. Division of Hematology, Department of Internal Medicine II, University of Wuerzburg, Germany
    • Battegay, Manuel. Division of Infectious Diseases and Hospital Epidemiology, Departments of Biomedicine and Clinical Research
    • Passweg, Jakob. Division of Hematology, University Hospital of Basel, Switzerland
    • Khanna, Nina. Infection Biology Laboratory, Department of Biomedicine
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2015, vol. 211, no. 8, p. 1251-1261. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:300624
    Summary
    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