title: Induction of Thelper1-driven antiviral T-cell lines for adoptive immunotherapy is determined by differential expression of IFN-γ and T-cell activation markers.
abstract: Viral infections with cytomegalovirus (CMV) or human adenovirus (HAdV) after stem cell transplantation are still associated with a high morbidity and mortality. Transfer of T-cell immunity from a healthy individual to a stem cell transplant recipient, known as adoptive T-cell transfer, has been shown to be effective to prevent viral complications. Treatment efficacy will depend on the availability of functional T-cell lines with a strong T(helper)1 response. Ex vivo isolation of antigen-specific T cells could be performed on the basis of the cytokine capture technique or antigen-induced expression of activation markers. In this study, we compare the specificity, expansion/differentiation potential, and T(helper)1 response against CMV and HAdV after different isolation strategies. Antigen-specific T cells from healthy donors were isolated by antigen-induced expression of IFN-γ and/or CD137 after stimulation with the viral antigens hexon (HAdV) or pp65 (CMV). Isolation of antigen-specific T cells based on the expression of activation markers is feasible and less time consuming, but in contrast to isolation based on IFN-γ secretion, it leads to a reduction of T(helper)1 cells. Both isolated CD137(+) and isolated IFN-γ(+) T cells mainly consist of CD4(+) T(CentralMemory) and T(EffectorMemory) cells with high expansion potential and effective cytokine production. CD154(+) is mainly expressed on CD4(+)T cells and shows coexpression with IFN-γ on activated T cells, which cannot be found for CD137(+) cells. In conclusion, T-cell lines could be easily generated on the basis of IFN-γ(+) and/or expression of the activation marker CD137 but both approaches result in different T-cell populations, which may lead to divergent T-cell responses in vivo.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Children's Hospital Tübingen, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Leibold
authors.forename: Judith
authors.initials: J
authors.lastname: Feucht
authors.forename: Ameli
authors.initials: A
authors.lastname: Halder
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Simone
authors.initials: S
authors.lastname: Kayser
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D016516:CD4-CD8 Ratio; D023201:CD40 Ligand / Q000378:metabolism; D036022:Capsid Proteins / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D010750:Phosphoproteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D010750:Phosphoproteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C018315:hexon capsid protein, Adenovirus; D023201:CD40 Ligand; D007371:Interferon-gamma