RT Journal Article
SR Electronic
T1 iNKT cells coordinate immune pathways to enable engraftment in nonconditioned hosts
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000999
DO 10.26508/lsa.202000999
VO 4
IS 7
A1 Nicholas J Hess
A1 Nikhila S Bharadwaj
A1 Elizabeth A Bobeck
A1 Courtney E McDougal
A1 Shidong Ma
A1 John-Demian Sauer
A1 Amy W Hudson
A1 Jenny E Gumperz
YR 2021
UL https://www.life-science-alliance.org/content/4/7/e202000999.abstract
AB 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.