Selective Manipulation of T Cell Subsets in Allogeneic Stem Cell Grafts to Reduce GVHD while Retaining GVT and Pathogen-Specific Immunity

Strategies being developed to modify the T cell content of allogeneic stem cell grafts include: a) depletion of the T_N subset of cells that contain the repertoire of T cells capable of recognizing minor histocompatibility antigens expressed on skin, gastrointestinal, and hepatic tissues; b) expanding T_REG cells that interfere with activation of alloreactive T cells to augment the stem cell graft; c) isolation and expansion of tumor-reactive T cells from naïve T cell progenitors for adoptive immunotherapy to augment the GVT effect; and d) retention of T_M cells in the graft to restore protective T cell immunity to pathogens.