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In vitro activation of CMV-specific human CD8(+) T cells by adenylate cyclase toxoids delivering pp65 epitopes
J. Jelinek, I. Adkins, Z. Mikulkova, J. Jagosova, R. Pacasova, S. Michlickova, P. Sebo, J. Michalek
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NS9871
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
Free Medical Journals
from 1997 to 1 year ago
Freely Accessible Science Journals
from 1997 to 1 year ago
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Medline Complete (EBSCOhost)
from 1997-01-01 to 2015-11-30
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
PubMed
21441962
DOI
10.1038/bmt.2011.68
Knihovny.cz E-resources
- MeSH
- Adenylyl Cyclases genetics immunology MeSH
- Lymphocyte Activation MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Cytomegalovirus immunology MeSH
- Epitopes, T-Lymphocyte immunology MeSH
- Phosphoproteins immunology MeSH
- Humans MeSH
- Peptide Fragments genetics immunology MeSH
- Viral Matrix Proteins immunology MeSH
- Amino Acid Sequence MeSH
- Cytomegalovirus Vaccines genetics immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Human CMV infects between 50-85% of healthy individuals and can cause live-threatening infections in immunocompromised patients. Therefore, peptide vaccination is being developed as a promising immunotherapeutic approach for treatment of patients at risk of CMV disease. The enzymatically inactive toxoid of Bordetella adenylate cyclase (CyaA-AC(-)) was shown to be an efficient tool for delivery of peptide epitopes and stimulation of Ag-specific T-cell immune responses. We investigated here the capacity of two CyaA-AC(-) constructs to deliver epitopes derived from the CMV phosphoprotein pp65 for activation of human T cells in vitro. Expansion of γ-IFN-secreting CMV-specific CD8(+) T cells, as well as increase of total IFN-γ and TNF-α production by PBMCs from CMV-seropositive donors were observed after in vitro stimulation with CyaA-AC(-) constructs carrying CMV epitopes, whereas limited activation of immune response occurred with free peptides. The activation of immune response was confirmed by expansion of CMV-specific T-cell clones and anti-CMV cytotoxic effect of stimulated PBMCs. These data open the way to clinical evaluation of CyaA-AC(-) constructs as tools for detection and expansion of CMV-specific T-cell immune responses for diagnostic and immunotherapeutic applications against CMV-associated diseases.
Cell and Molecular Microbiology Division Institute of Microbiology ASCR v v i Prague Czech Republic
Transfusion Department and Blood Bank of Brno Faculty Hospital Brno Czech Republic
References provided by Crossref.org
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