Modulation of CD8 T cell responses to AAV vectors with IgG-derived MHC class II epitopes
| Autor: | Mustafa N. Yazicioglu, Leslie P. Cousens, Federico Mingozzi, Robert J. Davidson, Daniel J. Hui, Jonathan D. Finn, Virginia Haurigot, Gary C. Pien, Yifeng Chen, David W. Scott, Anne S. De Groot, Shangzhen Zhou, Etiena Basner-Tschakarjan, George Buchlis, Alex Tai |
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| Přispěvatelé: | Technologies et systèmes d'information pour les agrosystèmes (UR TSCF), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Department of Applied Mathematics [Hong Kong], The Hong Kong Polytechnic University [Hong Kong] (POLYU), Immunologie moléculaire et biothérapies innovantes (IMBI), Généthon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Évry-Val-d'Essonne (UEVE)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Regulatory T cell
T cell viruses [SDV]Life Sciences [q-bio] Epitope 03 medical and health sciences 0302 clinical medicine Antigen Drug Discovery Genetics medicine Cytotoxic T cell IL-2 receptor Molecular Biology 030304 developmental biology Pharmacology 0303 health sciences MHC class II biology Molecular biology 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Molecular Medicine CD8 |
| Zdroj: | Molecular Therapy Molecular Therapy, Cell Press, 2013, ⟨10.1038/mt.2013.166⟩ Molecular Therapy, 2013, ⟨10.1038/mt.2013.166⟩ |
| ISSN: | 1525-0016 1525-0024 |
| DOI: | 10.1038/mt.2013.166⟩ |
| Popis: | International audience; Immune responses directed against viral capsid proteins constitute a main safety concern in the use of adeno-associated virus (AAV) as gene transfer vectors in humans. Pharmacological immunosuppression has been proposed as a solution to the problem; however, the approach suffers from several potential limitations. Using MHC class II epitopes initially identified within human IgG, named Tregitopes, we showed that it is possible to modulate CD8+ T cell responses to several viral antigens in vitro. We showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen-specific fashion, through a mechanism that seems to require cell-to-cell contact. Expression of a construct encoding for the AAV capsid structural protein fused to Tregitopes resulted in reduction of CD8+ T cell reactivity against the AAV capsid following immunization with an adenoviral vector expressing capsid. This was accompanied by an increase in frequency of CD4+CD25+FoxP3+ T cells in spleens and lower levels of inflammatory infiltrates in injected tissues. This proof-of-concept study demonstrates modulation of CD8+ T cell reactivity to an antigen using regulatory T cell epitopes is possible.Molecular Therapy (2013); doi:10.1038/mt.2013.166. |
| Databáze: | OpenAIRE |
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