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Leibold J.,University of Tübingen | Feucht J.,University of Tübingen | Halder A.,University of Tübingen | Stevanovic S.,University of Tübingen | And 4 more authors.
Journal of Immunotherapy | Year: 2012

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 Thelper1 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 Thelper1 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 Thelper1 cells. Both isolated CD137 + and isolated IFN-γ T cells mainly consist of CD4 + TCentralMemory and TEffectorMemory 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. © 2012 by Lippincott Williams & Wilkins.

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