[4][5][6] The establishment and maintenance of self-tolerance is an essential property of an immune system designed to eliminate foreign substances.
Veto activity is thought to be a form of antigen-specific suppression that maintains continuous self-tolerance.
[5] Veto-induced tolerance can be established in vitro and in vivo for both MHC class I and II as well as minor histocompatibility antigens.
This means that the addition of donor-veto cells to the donor graft can act as a specific immunosuppressant, only eliminating the cells that mediate graft rejection, but the rest of the T cellclone s (those that do not recognize the donor MHC/antigen) can provide immunity to the host normally.
[7][16] The large number of veto cells helped overcome the graft rejection that was mediated by the host CD8 T-cell precursors.
These are called reduced intensity or non-myeloablative conditioning regimens and since these protocols do not completely abolish the immune system of the host, Graft rejection is the main problem.
By expanding naïve CD8 T cells against 3rd-party stimulators under cytokine deprivation, clones that are reactive against the host are eliminated due to lack of nutrients and signaling.
Transfer of these Anti-3rd party Tcm with megadose TCD HSCT in preclinical models was successful at preventing graft rejection without GVHD under reduced intensity conditioning.
One study shows that this could be an effective solution for the production of off-the-shelf CAR T cells that will not be rejected or cause GvHD.