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Development of specific immunotherapies to prevent graft rejection and graft-versus-host disease offers the promise of selectively deleting only allospecific immune responses. Veto activity is the ability of a cell to specifically suppress/delete only T cells directed against antigens of the veto cells themselves, but not against third-party antigens. In the present study, we reasoned that providing TCR-like signaling to allogeneic major histocompatibility complex (MHC) molecules on the surface of CD8+ CTLs might result in enhanced veto function. To generate the donor antigen specific veto cells, we have utilized the Chimeric Antigen Receptor (CAR) T cell approach, in which CD8+ CTLs express an MHC alloantigen fused to signaling molecule apparatuses. We fused mouse MHC class I alloantigen (H-2D d) to the hinge and trans-membrane domains of the mouse CD8 chain plus intracellular signaling sequences …