Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity

J Immunol. 2005 Oct 15;175(8):5095-103. doi: 10.4049/jimmunol.175.8.5095.

Abstract

Human embryonic stem cells (hESCs) provide a unique resource to analyze early stages of human hematopoiesis. However, little is known about the ability to use hESCs to evaluate lymphocyte development. In the present study, we use a two-step culture method to demonstrate efficient generation of functional NK cells from hESCs. The CD56(+)CD45(+) hESC-derived lymphocytes express inhibitory and activating receptors typical of mature NK cells, including killer cell Ig-like receptors, natural cytotoxicity receptors, and CD16. Limiting dilution analysis suggests that these cells can be produced from hESC-derived hemopoietic progenitors at a clonal frequency similar to CD34(+) cells isolated from cord blood. The hESC-derived NK cells acquire the ability to lyse human tumor cells by both direct cell-mediated cytotoxicity and Ab-dependent cellular cytotoxicity. Additionally, activated hESC-derived NK cells up-regulate cytokine production. hESC-derived lymphoid progenitors provide a novel means to characterize specific cellular and molecular mechanisms that lead to development of specific human lymphocyte populations. These cells may also provide a source for innovative cellular immune therapies.

Publication types

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

MeSH terms

  • Cell Differentiation / physiology
  • Cell Line
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic*
  • Down-Regulation / physiology
  • Flow Cytometry
  • Hematopoiesis / immunology
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Receptors, Immunologic / physiology*
  • Stem Cells / cytology
  • Stem Cells / immunology*
  • Stem Cells / metabolism*
  • Up-Regulation / immunology

Substances

  • Cytokines
  • Receptors, Immunologic