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Rapamycin and MPA, But Not CsA, Impair Human NK Cell Cytotoxicity Due to Differential Effects on NK Cell Phenotype
Author(s) -
Eissens D. N.,
Van Der Meer A.,
Van Cranenbroek B.,
Preijers F. W. M. B.,
Joosten I.
Publication year - 2010
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2010.03242.x
Subject(s) - flow cytometry , cytokine , transplantation , interleukin 12 , k562 cells , immunology , cytolysis , cytotoxicity , cell , biology , cancer research , microbiology and biotechnology , in vitro , medicine , cytotoxic t cell , leukemia , biochemistry , genetics
Cyclosporin A (CsA), rapamycin (Rapa) and mycophenolic acid (MPA) are frequently used for GVHD prophylaxis and treatment after allogeneic stem cell transplantation (SCT). As NK cells have received great interest for immunotherapeutic applications in SCT, we analyzed the effects of these drugs on human cytokine‐stimulated NK cells in vitro . Growth‐kinetics of CsA‐treated cultures were marginally affected, whereas MPA and Rapa severely prevented the outgrowth of CD56 bright NK cells. Single‐cell analysis of NK cell receptors using 10‐color flow cytometry, revealed that CsA‐treated NK cells gained a similar expression profile as cytokine‐stimulated control NK cells, mostly representing NKG2A + KIR − NCR + cells. In contrast, MPA and Rapa inhibited the acquisition of NKG2A and NCR expression and NK cells maintained an overall NKG2A − KIR + NCR +/− phenotype. This was reflected in the cytolytic activity, as MPA‐ and Rapa‐treated NK cells, in contrast to CsA‐treated NK cells, lost their cytotoxicity against K562 target cells. Upon target encounter, IFN‐γ production was not only impaired by MPA and Rapa, but also by CsA. Overall, these results demonstrate that CsA, MPA and Rapa each have distinct effects on NK cell phenotype and function, which may have important implications for NK cell function in vivo after transplantation.