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International Immunology Advance Access originally published online on March 26, 2009
International Immunology 2009 21(5):599-606; doi:10.1093/intimm/dxp029
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs

Barbara Morandi1, Lorenzo Mortara2, Paolo Carrega3,4, Claudia Cantoni4, Gregorio Costa1, Roberto S. Accolla2, Maria Cristina Mingari3,5, Silvano Ferrini5, Lorenzo Moretta3,4,6 and Guido Ferlazzo1

1 Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
2 Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy
3 Department of Experimental Medicine, University of Genoa, Genoa, Italy
4 Istituto Giannina Gaslini, Genoa, Italy
5 Department of Experimental Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
6 Centro di Eccellenza Ricerca Biomedica, University of Genoa, Genoa, Italy

Correspondence to: G. Ferlazzo; E-mail: guido.ferlazzo{at}unime.it

NK cell recognition of cells that do not express or express low amounts of MHC class I molecules results not only in direct killing of target cells but also in the generation of specific T cell responses consequent to the induction of dendritic cell (DC) activation. While IL-12 production by NK cell-activated DCs is generally thought to play a critical role, a similar DC-mediated NK cell help has been reported also in IL-12-knockout mice. Here, we show that human NK cells can induce on DC surface membrane, via IFN-{gamma} secretion, the expression of high levels of IL-15. Remarkably, we show that DC expression of this membrane-bound form of IL-15, which is only partially associated with IL-15R molecules, is essential to promote specific CD8+ T lymphocyte response in the absence of DC-derived IL-12.

Keywords: CD8 lymphocytes, dendritic cells, IL-15 receptor alpha, membrane-bound IL-15, NK cells

Transmitting editor: E. Vivier

Received 1 October 2008, accepted 26 February 2009.


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