Reconstitution models to evaluate natural killer T cell function in tumor control

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11 Citas (Scopus)

Resumen

Natural killer T (NKT) cells are glycolipid-reactive T lymphocytes that function in immunosurveillance and immune regulation. However, reduced tumor control in NKT cell-deficient Jα18-/- mice may be confounded by an overall reduction in T-cell receptor (TCR) repertoire diversity in these animals. Mechanistic studies are also hindered by a lack of tools to target molecules specifically in NKT cells. To address these issues, we developed protocols to expand functional NKT cells and stably reconstitute them in Jα18-/- mice. In vivo delivery of α-galactosylceramide (α-GalCer)-loaded dendritic cells expanded NKT cells in wild-type mice without skewing CD4 or TCR Vβ expression profiles. Expanded NKT cells exhibited enhanced cytokine responses upon re-stimulation with glycolipid or CD3 ligation. Adoptive transfer of recently expanded wild-type or interferon (IFN)-γ-/- NKT cells protected recipient Jα18-/- mice from B16 melanoma metastasis without the need for additional glycolipid stimulation. However, NKT cell reconstitution in recipient Jα18-/- mice was short lived. Long-term reconstitution was only achieved when expanded NKT cells were transferred into sublethally irradiated recipients. Thirty days after transfer, NKT cell numbers, phenotype and α-GalCer-induced cytokine responses were equivalent to naive wild-type mice. Jα18-/- recipients reconstituted with wild-type or IFN-γ-/- NKT cells were both protected from B16 melanoma metastasis following α-GalCer treatment, and NK cell transactivation was intact in mice reconstituted with IFN-γ-/- NKT cells. These studies validate the use of reconstitution protocols to investigate the mechanisms of NKT cell immune function, demonstrating that NKT cell-derived IFN-γ and the altered TCR repertoire in Jα18-/- mice do not impact NKT cell-mediated antitumor responses.

Idioma originalEnglish
Páginas (desde-hasta)90-100
Número de páginas11
PublicaciónImmunology and Cell Biology
Volumen94
N.º1
DOI
EstadoPublished - ene. 1 2016

Nota bibliográfica

Publisher Copyright:
© 2016 Australasian Society for Immunology Inc. All rights reserved.

ASJC Scopus Subject Areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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