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iNKT cells coordinate immune pathways to enable engraftment in nonconditioned hosts. Life Sci Alliance 2021 Jul;4(7)

Date

06/12/2021

Pubmed ID

34112724

Pubmed Central ID

PMC8200291

DOI

10.26508/lsa.202000999

Scopus ID

2-s2.0-85108045175 (requires institutional sign-in at Scopus site)   5 Citations

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.

Author List

Hess NJ, S Bharadwaj N, Bobeck EA, McDougal CE, Ma S, Sauer JD, Hudson AW, Gumperz JE

Author

Amy W. Hudson PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigen-Presenting Cells
Cytokines
Female
Fetal Blood
Humans
Immunity, Innate
Immunotherapy
Lymphocyte Activation
Mice
Mice, Inbred NOD
Natural Killer T-Cells
Tissue Transplantation
Transplantation Immunology