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Stimulation of human EBV-and CMV-specific cytolytic effector function using allogeneic HLA molecules
Journal article   Peer reviewed

Stimulation of human EBV-and CMV-specific cytolytic effector function using allogeneic HLA molecules

L.J. D'Orsogna, H. van den Heuvel, E.M.W. van der Meer-Prins, D.L. Roelen, I.I.N. Doxiadis and F.H.J. Claas
The Journal of Immunology, Vol.189(10), pp.4825-4831
2012
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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 virusspecific 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*44:0 - 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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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.6 Immunology
1.6.127 T Cell Regulation
Web Of Science research areas
Immunology
ESI research areas
Immunology
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