Pathophysiology of mature BM lymphocytes in HSCT. (A) In HSCT, donor BM CD8⁺ T cells support HSC engraftment by facilitating HSC entry into the BM, inhibiting their exit, and suppressing host-derived alloreactive (allo-) BM CD4⁺ and CD8⁺ T cells. NKT cells are resistant to irradiation, a common conditioning regimen in HSCT, leading to an altered NKT-cell/T-cell balance in the BM and IL-4 production by host BM NKT cells. This results in Th2-polarization of donor BM T cells and induction of IL-10–producing donor BM Tregs, which improve HSC engraftment. Moreover, donor BM Tregs preferentially accumulate around donor HSCs and provide immune protection. In addition, they promote B-cell reconstitution by facilitating IL-7 production from BM perivascular stromal cells. High numbers of donor-derived CD27⁺ γδ T cells post-HSCT correlate with longer disease-free survival, but the exact localization of those cells, and whether they home to the BM, is not known. (B) GVHD is mediated by activated donor T cells and is a major cause of morbidity and mortality after HSCT. High levels of naïve and central-memory allo-CD8⁺ T cells correlate with increased GVHD risk. Donor BM allo-CD8⁺ T cells can induce host plasma cell destruction. In addition, activated donor CD8⁺ T cells likely negatively affect HSCs in GVHD through secretion of proinflammatory cytokines, including TNF-α and IFN-γ. Moreover, donor-derived alloantibodies, presumably secreted by plasma cells in BM, can promote cutaneous chronic GVHD. Host BM NKT cells can ameliorate GVHD by inhibiting the proliferation and preventing the activation of allo-CD8⁺ and CD4⁺ T cells. Finally, donor-derived CD8⁺ γδ T cells are associated with higher incidences of GVHD, but the role of BM in this process is unknown.