Summary of cell interactions and molecular products that prevent rejection of combined donor hematopoietic cell and organ transplants after conditioning with TLI and ATS. Lymphoid tissue radiation induces massive cell death and generation of apoptotic bodies that are recognized by host CD8⁺ DC receptors including Tim-4, DEC205, SIRPα, and Treml4. After TLI, the DCs become “tolerogenic” with IDO production, and upregulate surface molecules CD1d, Rae-1, and PDL-2 that interact with TCR, NKG2D, and PD-1 receptors on host NKT cells. NKT cells polarize their cytokine production toward IL-4, and interact with host Tregs to upregulate PD-1 and polarize their cytokine production toward IL-10. The “tolerogenic” NKT cells also activate host MDSCs to upregulate PDL-1 and IL-4Rα, and to secrete arginase-1. Activated innate and adaptive host immune cells suppress rejection by host Tcons, and promote chimerism and organ graft acceptance. HCT, hematopoietic cell transplantation.