Stimulation of human EBV- and CMV-specific cytolytic effector function using allogeneic HLA molecules.
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.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden 2300 RC, The Netherlands. Lloyd.dorsogna@health.wa.gov.au
Lloyd J
LJ
D'Orsogna
Heleen
H
van den Heuvel
Ellen M W
EM
van der Meer-Prins
Dave L
DL
Roelen
Ilias I N
II
Doxiadis
Frans H J
FH
Claas
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D015235:HLA-B Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D015235:HLA-B Antigens; D010455:Peptides; D014764:Viral Proteins