OBJECTIVE: Cytokine-induced killer cells (CIK) are CD3(+)CD56(+) T cells with natural killer (NK)-like cytotoxic activity used for the immunotherapy of tumors. We aimed to fully characterize CIK cells and define their ontogeny. MATERIALS AND METHODS: CIK were generated in vitro by stimulation of peripheral blood mononuclear cells or T-cell subsets with interferon-gamma, anti-CD3 and interleukin-2. They were fully characterized in terms of phenotype, cytotoxic activity, and gene expression with respect to circulating CD3(+)CD56(+) cells, NK cells, and CD56(-) T cells present in CIK cultures. RESULTS: We demonstrate that CIK are terminally differentiated CD8 T cells that derive from proliferating CD3(+)CD56(-)CD8(+) T cells. They express polyclonal T-cell receptor Vbeta chains and have acquired CD56, NKG2D, and large granular lymphocyte morphology, but lack expression of most NK-specific activating (NKp30, NKp44, NKp46) and inhibitory (KIR2DL1, KIR2DL2, KIR3DL1, NKG2A, CD94) receptors, and can kill K562 targets. Circulating CD3(+)CD56(+) cells are also CD8(+)CD16(-), but are oligoclonal, poorly cytotoxic for K562, and express lower levels of CD56 and NKG2D. Gene profiling of CIK, CD56(-) T and NK cells present at the end of culture shows that differences are much more limited between CIK and CD56(-) T compared to CIK and NK cells. Most of the genes upregulated in CIK cells compared to CD56(-) T cells are part of the tumor necrosis factor gene network. CONCLUSIONS: The CIK phenotype, that is CD45RA(+), CCR7(-), CD62L-weakly positive, CD11a(+), CD27(+), CD28(-), macrophage inflammatory protein 1alpha(+), perforin(+), Fas ligand(+) coincides almost exactly with that described for the T RA(+) effector memory CD27 single positive subset of terminally differentiated human memory T cells.
OBJECTIVE: Cytokine-induced killer cells (CIK) are CD3(+)CD56(+) T cells with natural killer (NK)-like cytotoxic activity used for the immunotherapy of tumors. We aimed to fully characterize CIK cells and define their ontogeny. MATERIALS AND METHODS: CIK were generated in vitro by stimulation of peripheral blood mononuclear cells or T-cell subsets with interferon-gamma, anti-CD3 and interleukin-2. They were fully characterized in terms of phenotype, cytotoxic activity, and gene expression with respect to circulating CD3(+)CD56(+) cells, NK cells, and CD56(-) T cells present in CIK cultures. RESULTS: We demonstrate that CIK are terminally differentiated CD8 T cells that derive from proliferating CD3(+)CD56(-)CD8(+) T cells. They express polyclonal T-cell receptor Vbeta chains and have acquired CD56, NKG2D, and large granular lymphocyte morphology, but lack expression of most NK-specific activating (NKp30, NKp44, NKp46) and inhibitory (KIR2DL1, KIR2DL2, KIR3DL1, NKG2A, CD94) receptors, and can kill K562 targets. Circulating CD3(+)CD56(+) cells are also CD8(+)CD16(-), but are oligoclonal, poorly cytotoxic for K562, and express lower levels of CD56 and NKG2D. Gene profiling of CIK, CD56(-) T and NK cells present at the end of culture shows that differences are much more limited between CIK and CD56(-) T compared to CIK and NK cells. Most of the genes upregulated in CIK cells compared to CD56(-) T cells are part of the tumor necrosis factor gene network. CONCLUSIONS: The CIK phenotype, that is CD45RA(+), CCR7(-), CD62L-weakly positive, CD11a(+), CD27(+), CD28(-), macrophage inflammatory protein 1alpha(+), perforin(+), Fas ligand(+) coincides almost exactly with that described for the T RA(+) effector memory CD27 single positive subset of terminally differentiated human memory T cells.
Authors: I Pizzitola; F Anjos-Afonso; K Rouault-Pierre; F Lassailly; S Tettamanti; O Spinelli; A Biondi; E Biagi; D Bonnet Journal: Leukemia Date: 2014-02-07 Impact factor: 11.528
Authors: Selim Kuçi; Eva Rettinger; Bernhard Voss; Gerrit Weber; Miriam Stais; Hermann Kreyenberg; Andre Willasch; Zyrafete Kuçi; Ewa Koscielniak; Stephan Klöss; Dorothee von Laer; Thomas Klingebiel; Peter Bader Journal: Haematologica Date: 2010-04-07 Impact factor: 9.941
Authors: Leonard Christopher Schmeel; Frederic Carsten Schmeel; Christoph Coch; Ingo G H Schmidt-Wolf Journal: J Cancer Res Clin Oncol Date: 2014-11-08 Impact factor: 4.553