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International Immunology Advance Access published online on February 28, 2008
International Immunology, doi:10.1093/intimm/dxn014
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Methylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells

Chiara Vitale1,*, Francesca Cottalasso1,*, Elisa Montaldo1, Lorenzo Moretta1,2,3 and Maria Cristina Mingari1,2,3,4

1 Dipartimento Medicina Sperimentale, Università di Genova, Genova, Italy
2 Istituto Giannina Gaslini, Genova, Italy
3 Centro di Eccellenza per le Ricerche Biomediche, Università di Genova, Genova, Italy
4 Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

Correspondence to: Correspondence to: C. Vitale, Immunologia laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova, Italy; E-mail: chiara.vitale{at}istge.it

Previous studies showed that methylprednisolone (MePDN) down-regulates the surface expression of activating NK receptors and sharply inhibits the NK cytotoxicity both in vitro and in vivo. Since MePDN is administered to patients undergoing hemopoietic stem cell transplant to treat acute graft versus host disease (GvHD), we analyzed whether it could also inhibit the NK cell differentiation from CD34+ hemopoietic cell precursors, thus interfering with the development of effector cells with anti-leukemic potential. We show that MePDN promotes the in vitro differentiation of CD161+CD56+/– immature NK cells by inducing a rapid expression of NKp46, NKG2D, DNAX-accessory molecule 1 (DNAM-1), leukocyte function-associated antigen-1 and NKG2A and an efficient cytolytic activity. This phenotypic and functional NK cell maturation occurred more rapidly than in parallel control cultures performed in the absence of MePDN. In addition, MePDN induced CD33+CD161–CD56– myeloid precursors to switch toward NK cells. It is also of note that immature NK cells when cultured in the absence (but not in the presence) of MePDN produced high amounts of IL-8. These data indicate that MePDN can accelerate the in vitro NK cell differentiation, thus revealing a dichotomous effect on immature versus mature NK cells; in addition, interference with the in vitro development of myeloid cells occurred. These effects should be further investigated in hemopoietic stem cell transplanted patients receiving steroids to treat GvHD.

Keywords: glucocorticoids, lymphocyte differentiation, NK cells

* These authors contributed equally to this study.

Transmitting editor: E. Vivier

Received 22 November 2007, accepted 23 January 2008.


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