Faculty Collaboration Database

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)   6 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

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