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| Article Authors: | Lloyd J D'Orsogna; Heleen van den Heuvel; Ellen M W van der Meer-Prins; Dave L Roelen; Ilias I N Doxiadis; Frans H J Claas |
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| Article Title: | Stimulation of Human EBV- and CMV-Specific Cytolytic Effector Function Using Allogeneic HLA Molecules. |
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| Reference ID: | 1025244 |
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| Abstract: | Viral infection is a major cause of morbidity and mortality, and there are few therapeutic options available to augment a virus-specific T cell response. Although allo-HLA cross-reactivity from virus-specific memory T cells is common, it is unclear whether priming with specific allogeneic cells could conversely elicit a viral peptide/self-HLA restricted cytotoxic T cell response in humans. First, we used the previously described allo-HLA-B*44:02 cross-reactivity of EBV peptide/HLA-B8 restricted T cells, to determine whether allogeneic HLA stimulation can elicit a cytolytic immune response against EBV. HLA-B8(+) HLA-B44(-) EBV-seropositive PBMCs were stimulated with either HLA-B*44:02(+) or HLA-B*44:03(+) mismatched irradiated PBMCs in a 7-10 d MLR. The allo-HLA stimulated responder cells were then evaluated for cytotoxicity using EBV peptide loaded autologous target cells and unloaded HLA-B8(+) EBV LCL target cells. PBMCs from EBV-seropositive donors gained EBV-specific cytolytic effector function following specific allo-HLA stimulation. Finally, we also elicited cytolytic CMV-specific responses using specific allogeneic cell stimulation, to confirm that this technique can be used to elicit viral peptide/self-HLA restricted responses even from nonpublic TCR responses. Allogeneic cell stimulation used as a cell therapy may be a potential tool to augment an antiviral T cell response in patients with EBV or CMV infection. |
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| Affiliations: | Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden 2300 RC, The Netherlands; |
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| Date: | 2012 |
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| Reference Type: | Literature |
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| PubMed ID: | 23077240 |
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| Journal: | J Immunol |
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| Journal Volume: | 189 |
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| Article Pages: | 4825-31 |
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| Journal ISSN: | 1550-6606 |
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| Curation Last Updated: | 2012-12-04 20:01:02 |
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