Hematopoietic stem cell transplantation across major genetic barriers: tolerance induction by megadose CD34 cells and other veto cells.

Studies in mice and humans demonstrate that transplantation of hematopoietic progenitors in numbers larger than commonly used overcomes major genetic barriers. In vitro studies suggest that veto cells, within the population of hematopoietic progenitors, facilitate this favorable outcome. Tolerance induction can be further enhanced by other veto cells. Perhaps the most potent veto cell is the CD8(+) CTL. However, this cell is also associated with marked GVHD, which can be separated from the veto activity by generating anti-third party CTLs under IL-2 deprivation.