title: EBV-specific CD4+ T cell clones exhibit vigorous allogeneic responses.
abstract: Alloreactive T cells play a key role in mediating graft-vs-host disease and allograft rejection, and recent data suggest that most T cell alloreactivity resides within the CD4 T cell subset. Particularly, T cell responses to herpesvirus can shape the alloreactive repertoire and influence transplantation outcomes. In this study, we describe six distinct EBV-specific CD4(+) T cell clones that cross-reacted with EBV-transformed lymphoblastoid cell lines (LCLs), dendritic cells, and endothelial cells expressing MHC class II alleles commonly found in the population. Allorecognition showed exquisite MHC specificity. These CD4(+) T cell clones efficiently killed dendritic cells or LCLs expressing the cross-reactive allogeneic MHC class II molecules, whereas they did not kill autologous LCLs. Endothelial cells expressing the proper allogeneic MHC molecules were poorly killed, but they induced high-level TNF-alpha production by the EBV-specific CD4(+) T cell clones. As already proposed, the strong alloreactivity toward LCLs suggest that these cells could be used for selective depletion of alloreactive T cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 601, Institut de Biologie, Nantes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Landais
authors.forename: Alexis
authors.initials: A
authors.lastname: Morice
authors.forename: Heather M
authors.initials: HM
authors.lastname: Long
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Haigh
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.forename: Graham S
authors.initials: GS
authors.lastname: Taylor
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Houssaint
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002144:Callithrix; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology
chemical_list: D007519:Isoantigens