Immunoregulatory cells for transplantation tolerance and graft-versus-leukemia effect

Abstract

Various immunoregulatory cells that inhibit graft-versus-host disease (GVHD) and induce the graft-versus-leukemia (GVL) effect are found after allogeneic hematopoietic stem cell transplantation. These cells comprise CD4+CD25+ regulatory T-cells, regulatory dendritic cells (rDCs), gamma(delta) T-cells, natural killer (NK) T-cells, and NK cells and T-cells with inhibitory NK receptors. Although the first 4 types of cells effectively inhibit GVHD in animal models, with rDCs showing an inhibitory effect on GVHD in humans as well, the GVL effect was observed only in rDCs. Additional analyses are required to determine whether these cells can inhibit GVHD and exert the GVL effect in humans. In contrast, NK cells and T-cells with inhibitory NK receptors have been shown in humans to possess a suppressive activity against GVHD while preserving the GVL effect. These results indicate that immunoregulatory cells may be used to modulate GVHD and the GVL effect in clinical settings.