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Life Sci Alliance ; 4(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34112724

RESUMO

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.


Assuntos
Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Imunologia de Transplantes/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Citocinas/imunologia , Feminino , Sangue Fetal/imunologia , Humanos , Imunidade Inata/imunologia , Imunoterapia/métodos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos NOD , Transplante de Tecidos/métodos
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