Stimulation of human EBV-and CMV-specific cytolytic effector function using allogeneic HLA molecules
D'Orsogna, L.J., van den Heuvel, H., van der Meer-Prins, E.M.W., Roelen, D.L., Doxiadis, I.I.N. and Claas, F.H.J. (2012) Stimulation of human EBV-and CMV-specific cytolytic effector function using allogeneic HLA molecules. The Journal of Immunology, 189 (10). pp. 4825-4831.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||American Association of Immunologists|
|Copyright:||© 2012 by The American Association of Immunologists, Inc|
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