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Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes
- Publication Year :
- 2009
-
Abstract
- 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 V beta 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, KIR3DLI, 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 1 alpha(+), 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. (c) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
- Subjects :
- Cancer Research
Lymphocyte
chemical and pharmacologic phenomena
Biology
CD8-Positive T-Lymphocytes
Interleukin 21
Neoplasms
Genetics
medicine
Cytotoxic T cell
Humans
Killer Cells, Lymphokine-Activated
Molecular Biology
Cell Proliferation
Immunity, Cellular
Cytokine-induced killer cell
hemic and immune systems
Cell Differentiation
Cell Biology
Hematology
NKG2D
Natural killer T cell
Molecular biology
Antigens, Differentiation
medicine.anatomical_structure
Immunology
Interleukin 12
Immunotherapy
K562 Cells
Immunologic Memory
Cytokine-induced killer (CIK) cells
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6e120b2c0b6c2cd3be9aafec74f08e8a