Invariant natural killer T cells generated from human adult hematopoietic stem-progenitor cells are poly-functional

Cytokine. 2015 Mar;72(1):48-57. doi: 10.1016/j.cyto.2014.12.009. Epub 2015 Jan 5.

Abstract

Invariant natural killer T (iNKT) cells constitute an important subset of T cells that can both directly and indirectly mediate anti-tumor immunity. However, cancer patients have a reduction in both iNKT cell number and function, and these deficits limit the potential clinical application of iNKT cells for cancer therapy. To overcome the problem of limited iNKT cell numbers, we investigated whether iNKT cells can be generated in vitro from bone marrow-derived adult hematopoietic stem-progenitor cells (HSPC). Our data demonstrate that co-culture of HSPC with OP9-DL1 stromal cells, results in a functional CD3(+) T cell population. These T cells can be further differentiated into iNKT cells by secondary culture with CD1d-Ig-based artificial antigen-presenting cells (aAPC). Importantly, these in vitro-generated iNKT cells are functional, as demonstrated by their ability to proliferate and secrete IFN-γ and GM-CSF following stimulation.

Keywords: Adoptive immunotherapy; CD1d; NKT cells; Stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Presenting Cells / immunology
  • Antigens, CD1d / immunology
  • Cell Differentiation
  • Coculture Techniques
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Activation*
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Stromal Cells / immunology

Substances

  • Antigens, CD1d
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor