The use of donor-derived veto cells in hematopoietic stem cell transplantation.

The induction of immune tolerance by specific agents, as opposed to general immune suppression, is a most desirable goal in transplantation biology. One approach to attain this goal is afforded by the use of donor-derived cells endowed with veto activity, which is the ability of a cell to specifically suppress only T cells directed against its antigens. A megadose of purified veto CD34(+) hematopoietic stem cells is already used in patients to allow hematopoietic stem cells transplantation (HSCT) across major genetic barriers, while avoiding severe graft versus host disease (GVHD). However, allowing engraftment of such T cell-depleted HSCT under safer reduced intensity conditioning (RIC) protocols still remains a challenge. Therefore, combining megadose of CD34(+) HSCT with other GVHD-depleted veto cells could enable facilitation of engraftment of HSCT under RIC without the adverse complication of GVHD. This approach might provide a safer modality for enabling engraftment of HSCT, enabling its application in elderly patients who cannot tolerate intensive protocols and to a variety of patients with non-malignant disorders, associated with longer life expectancy, in whom the use of a high risk conditioning cannot be considered.