@article {Hesse202000999, author = {Nicholas J Hess and Nikhila S Bharadwaj and Elizabeth A Bobeck and Courtney E McDougal and Shidong Ma and John-Demian Sauer and Amy W Hudson and Jenny E Gumperz}, title = {iNKT cells coordinate immune pathways to enable engraftment in nonconditioned hosts}, volume = {4}, number = {7}, elocation-id = {e202000999}, year = {2021}, doi = {10.26508/lsa.202000999}, publisher = {Life Science Alliance}, abstract = {Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that interact with key antigen-presenting cells to modulate adaptive T-cell responses in ways that can either promote protective immunity, or limit pathological immune activation. Understanding the immunological networks engaged by iNKT cells to mediate these opposing functions is a key pre-requisite to effectively using iNKT cells for therapeutic applications. Using a human umbilical cord blood xenotransplantation model, we show here that co-transplanted allogeneic CD4+ iNKT cells interact with monocytes and T cells in the graft to coordinate pro-hematopoietic and immunoregulatory pathways. The nexus of iNKT cells, monocytes, and cord blood T cells led to the release of cytokines (IL-3, GM-CSF) that enhance hematopoietic stem and progenitor cell activity, and concurrently induced PGE2-mediated suppression of T-cell inflammatory responses that limit hematopoietic stem and progenitor cell engraftment. This resulted in successful long-term hematopoietic engraftment without pretransplant conditioning, including multi-lineage human chimerism and colonization of the spleen by antibody-producing human B cells. These results highlight the potential for using iNKT cellular immunotherapy to improve rates of hematopoietic engraftment independently of pretransplant conditioning.}, URL = {https://www.life-science-alliance.org/content/4/7/e202000999}, eprint = {https://www.life-science-alliance.org/content/4/7/e202000999.full.pdf}, journal = {Life Science Alliance} }