Журнал гематологии и тромбоэмболических заболеваний
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Veto-Engineering Immune Tolerance

Uwe D Staerz*, Janae W Cull, Yan Qi

The old veto effect may be moving from its status as an obscure immune inhibitory phenomenon to an important role on specific immune suppression. In today's clinical practice, broad suppression of the immune system is employed to avoid transplant rejection and mitigate auto-aggressive immune responses. Though highly effective, this approach impairs immune protection against infectious challenges. Therapeutic approaches are being sought that specifically inhibit sections of the immune system without affecting beneficial immune functions. One such tactic entails the classical veto-effect that employs donor-derived CD8+ T cells to inhibit cellular immune responses. Indeed, this kind of veto has already found applications as the underpinning of a more broadly applicable CAR-T cell therapy and of a more spec0069fic immune suppression for haploidentical Hematopoietic Stem Cell (HSC) transplantations. To broaden and simplify the use of veto, engineering strategies are discussed that affix its immune inhibitory function to cells of different tissues. They are based on the transfer of the CD8 α-chain to the surface of different cell populations. We predict that engineered veto will simplify specific immune suppression and broadening its application to organ transplantations and possibly the treatment of autoimmune diseases. It may represent an avenue to induce immunological tolerance.