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Measuring Antiviral Capacity of T Cell Responses to Adenovirus
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
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2019 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 202, no 2, p. 618-624Article in journal (Refereed) Published
Abstract [en]

Adenoviruses are a major cause of infectious mortality in children following allogeneic hematopoietic stem cell transplantation, with adoptive transfer of adenovirus-specific T cells being an effective therapeutic approach. We have previously shown that T cells specific for the peptide epitope LTDLGQNLLY were protective. In this study, we aimed to establish a viral dissemination assay to measure the antiviral capacity of T cells specific for this and other peptide epitopes in an infectious setting. We used replication-competent adenovirus 11 (Ad11pGFP) and adenovirus 5 containing adenovirus 35 fiber (Ad5F35GFP) viruses and T cells specific for HLA-A*01-restricted LTDLGQNLLY, HLA-B*07-restricted KPYSGTAYNAL, and HLA-A*02-restricted LLDQLIEEV peptide epitopes. T cells in PBMC from healthy donors were expanded with peptide and IL-2 or treated with IL-2 alone to serve as nonstimulated control cells, and then these expanded or nonstimulated CD8(+) cells were purified and cocultured with autologous monocytes infected with adenovirus at low multiplicity of infection. After 3 d, the number of infected GFP(+) monocytes and, hence, viral dissemination was quantified by flow cytometry. T cells expanded with LTDLGQNLLY peptide from multiple HLA-A*01(+) donors prevented adenovirus dissemination, and nonstimulated T cells did not prevent dissemination, thus, indicating that LTDLGQNLLY-specific T cells have high antiviral capacity. Similarly, expanded KPYSGTAYNAL- and LLDQLIEEV-specific T cells could prevent viral dissemination. However, the frequency of expanded T cells specific for these last two epitopes was variable between donors with consequent variable prevention of adenoviral dissemination. Taken together, we demonstrate that T cells specific for three peptide epitopes, from both structural and nonstructural proteins, can prevent adenoviral dissemination and provide a novel method to measure the antiviral capacity of adenovirus-specific T cell responses.

Place, publisher, year, edition, pages
American Association of Immunologists , 2019. Vol. 202, no 2, p. 618-624
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Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-155759DOI: 10.4049/jimmunol.1801003ISI: 000455041800032PubMedID: 30530481OAI: oai:DiVA.org:umu-155759DiVA, id: diva2:1283175
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved

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Mei, Ya-Fang

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