The unexpected effect of cyclosporin A on CD56+CD16- and CD56+CD16+ natural killer cell subpopulations

Hongbo Wang, Bartosz Grzywacz, David Sukovich, Valarie McCullar, Qing Cao, Alisa B. Lee, Bruce R. Blazar, David N. Cornfield, Jeffrey S. Miller, Michael R. Verneris

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Cyclosporin A (CSA) is commonly used to prevent graft-versus-host disease. The influence of CSA on T-cell function has been extensively investigated; however, the effect of CSA on natural killer (NK) cells is less understood. NK cells were cultured with IL-2 and IL-15 with and without CSA for 1 week. Compared with controls, CSA-treated cultures showed fewer CD56 +CD16+KIR+ NK cells and a reciprocal increase in CD56+CD16-KIR- cells. These changes were due mainly to a reduced proliferation of the CD56dim NK-cell subpopulation and a relative resistance of CD56bright NK cells to CSA. Following coculture with K562 targets, CSAexposed NK cells differed from controls and lacked Ca2+ oscillations, nuclear factor of activated T cells (NFAT) dephosphorylation, and NFAT nuclear translocation. NK cells cultured in CSA retained cytotoxicity against K562, Raji, and KIR ligand-expressing lymphoblastoid cells. NK cells cultured in CSA showed increases in NKp30 and reductions in NKp44 and NKG2D. Following IL-12 and IL-18 stimulation, CSA-treated NK cells showed more IFN-γ-producing cells. Using in vitro NK-cell differentiation, progenitor cells gave rise to more CD56 +KIR- NK cells in the presence of CSA than controls. Collectively, these studies show that CSA influences NK-cell function and phenotype, which may have important implications for graft-versus-leukemia effects.

Original languageEnglish (US)
Pages (from-to)1530-1539
Number of pages10
Issue number5
StatePublished - Sep 1 2007


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