NK cells in secondary lymphoid tissues
Natural Killer (NK) cells are part of the innate immune system. They are thought to limit viremia and tumor burden prior to the onset of adaptive immunity by T and B cells. NK cells have been initially described as peripheral blood lymphocytes that spontaneously lyse tumor and virus-infected cells.
Recently this paradigm, however, had to be revised and we contributed to this redefinition of NK cells. A large NK cell compartment was found in secondary lymphoid organs like lymph nodes, spleen and tonsils. Together with a small NK cell subset in peripheral blood these CD56brightCD16- NK cells lack cytolytic ability, but secrete promptly immunoregulatory cytokines upon activation. Longer activation matures NK cells of secondary lymphoid organs into the cytolytic NK cell population that predominates in blood.
These findings indicate that non-cytolytic NK cells are at least as frequent as the classical Natural Killers and require activation for their functions. Both are new unexpected features of NK cells, but offer the possibility to selectively activate NK cells for immunotherapy.
We and others have shown that dendritic cells can activate NK cells and are probably responsible for NK cell activation prior to the initiation of adaptive immunity. Furthermore, we have characterize some features of the immunological synapse mediating this NK activation by dendritic cells, and that NK cells activated in this fashion can restrict B cell transformation by EBV. We are now exploring an in vivo model of human immune system component reconstitution in severely immune compromised mice to analyze how these mechanisms contribute to EBV specific immune control.
Related articles from our laboratory:
1. Guido Ferlazzo, Ming L. Tsang, Lorenzo Moretta, Giovanni Melioli, Ralph M. Steinman and Christian Münz
Human dendritic cells activate resting NK cells and are recognized via the NKp30 receptor by activated NK cells. Journal of Experimental Medicine (2002), 195: 343-351
2. Guido Ferlazzo, Dolca Thomas, Shao-Lee Lin, Kiera Goodman, Barbara Morandi, William A. Muller, Allessandro Moretta and Christian Münz
The abundant NK cells in human secondary lymphoid tissues require activation to to express killer cell Ig-like receptors and become cytolytic. Journal of Immunology (2004), 172: 1455-1462
3. Guido Ferlazzo, Maggi Pack, Dolca Thomas, Casper Paludan, Dorothee Schmid, Till Strowig, Gwenola Bougras, William A. Muller, Lorenzo Moretta and Christian Münz
Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proceedings of the National Academy of Sciences of the United States of America (2004), 101: 16606-16611
4. Fabienne Brilot, Till Strowig, Susanne M. Roberts, Frida Arrey and Christian Münz
NK cell survival mediated through the regulatory synapse with human dendritic cells requires IL-15Ralpha. Journal of Clinical Investigation (2007), 117:3316-3329
5. Till Strowig, Fabienne Brilot, Frida Arrey, Gwenola Bougras Dolca Thomas, William A. Muller and Christian Münz
Tonsillar Natural Killer cells restrict Epstein-Barr virus-induced B cell transformation via IFN-gamma. PLoS Pathogens (2008), 4(2): e27