Raising the spectra of T-cell profiling.

creased risks of deleterious host-initiated and donor-initiated innate and adaptive immune responses. Administration of CpC oligonucleotides resulted in increased infiltration of lymphoid organs and Peyer patches by donor T cells in allogeneic recipients. The augmented alloreactivity was made manifest as increased GVHD and graft rejection, with the donor and host T cells activated by host-type and donor-type antigen-presenting cells (APCs), respectively, following toll-like receptor 9 (TLR9) ligand binding to APCs. Accelerated GVHD (but not graft rejection) was dependent on IFNsynthesis by T cells. Of note, bone marrow from donor mice deficient in CD80 or CD86 costimulatory molecules engrafted more efficiently after recipients received sublethal irradiation, supporting the role for donor APCs in activating host immunity and effector T cells that mediate graft rejection. The paper by Taylor et al represents part of an emerging paradigm that runs counter to existing dogma regarding the importance of host DCs rather than donor DCs in allogeneic transplantation. This report represents the first clear demonstration of an important effect of donor DCs, contained in the graft, in the regulation of host immune activation. Complementary studies from our own group have demonstrated a role for donor DCs in augmenting the alloreactivity of donor T cells and enhancing graft versus leukemia effects.3,4 Thus, it is time for donor DCs to take their turn in the dance of cell types involved in allogeneic transplantation. These donor cell populations are excellent targets for novel maneuvers in graft engineering designed to reduce graft rejection by reducing host T-cell activation or augment donor T-cell alloreactivity to increase graft versus leukemia effects. Conflict-of-interest disclosure: The authors declare no competing financial interests. ■