Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood.

Published

Journal Article

Previous studies have demonstrated that high concentrations of methyl-β-cyclodextrin (MβCD, 10-15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of MβCD (1-4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3(-)CD56(+) natural killer (NK) cells were the dominant subpopulation, and a significant dose-effect relationship existed between the proportion of NK cells and the concentration of MβCD. In the groups treated with 3-4 mM MβCD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with MβCD, CD69 was more preferentially expressed on CD3(-)CD56(+) cells than on CD3(+) cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. MβCD and IL-2 synergistically could also induce interferon-γ (IFN-γ) production in CD56(+) human PBMCs. Mechanistic studies revealed that IFN-γ production in response to MβCD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1β, and CD56(+)CD14(+) dendritic cell-like cells and B cells might mediate the ability of MβCD to activate NK cells. The MβCD-activated NK cells also had high cytotoxicity against the natural killer cell-sensitive K562 cells or lymphokine-activated killer cell-sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of MβCD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs.

Full Text

Cited Authors

  • Lü, H-Z; Zhu, A-Y; Chen, Y; Tang, J; Li, B-Q

Published Date

  • July 2011

Published In

Volume / Issue

  • 72 / 7

Start / End Page

  • 538 - 546

PubMed ID

  • 21540068

Pubmed Central ID

  • 21540068

Electronic International Standard Serial Number (EISSN)

  • 1879-1166

International Standard Serial Number (ISSN)

  • 0198-8859

Digital Object Identifier (DOI)

  • 10.1016/j.humimm.2011.03.022

Language

  • eng