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EBV-Specific CD4⁺ T Cell Clones Exhibit Vigorous Allogeneic Responses¹

Elise Landais^*, Alexis Morice^*, Heather M. Long, Tracey A. Haigh, Béatrice Charreau, Marc Bonneville^*, Graham S. Taylor and Elisabeth Houssaint^2,*

^* Institut National de la Santé et de la Recherche Médicale, Unité 601, Institut de Biologie, Nantes, France; Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom; and Institut National de la Santé et de la Recherche Médicale, Unité 643, Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France

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- 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.

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				L. K. Selin and M. A. Brehm Frontiers in Nephrology: Heterologous Immunity, T Cell Cross-Reactivity, and Alloreactivity J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2268 - 2277. [Abstract] [Full Text] [PDF]