Host donor-reactive T cell

Host donor-reactive T cells are recipient immune cells that recognize donor-derived antigens, primarily through the interaction of their T-cell receptors (TCR) with non-self Major Histocompatibility Complex (MHC) molecules (Miller, 1980). These cells are the primary mediators of graft rejection in organ and hematopoietic stem cell transplantation. The veto effect is a specialized mechanism of immune tolerance where specific donor-derived cells, known as veto cells, induce apoptosis in these host donor-reactive T cells upon recognition (Reisner et al., 2011). This process occurs when the host T cell's TCR binds to the MHC class I molecule on the veto cell, which then delivers a lethal signal to the host cell, often involving the CD8 molecule and Fas/FasL pathways (Reisner et al., 2011). Therapeutic strategies, such as the administration of donor-derived facilitating cells (e.g., FCR001) or CD8+ veto cells, aim to exploit this mechanism to achieve stable chimerism and long-term graft survival without the need for lifelong immunosuppression (Talaris Therapeutics, 2023). By selectively eliminating only the T-cell clones that react against the donor, the veto effect preserves the rest of the recipient's immune system, reducing the risk of infections and malignancies associated with broad immunosuppressive drugs (Medeor Therapeutics, 2023).

Other names

Host anti-donor T cellAlloreactive host T cellRecipient donor-specific T cellHost donor-reactive T cells recognizing veto cell MHC class I via TCR

Induction of clonal deletion and apoptosis in host T cells that recognize donor MHC class I via their TCR, mediated by the veto effect and back-signaling through the CD8 molecule.