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NK cells of 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. We are now investigating how DCs interact with NK cells of secondary lymphoid organs and how this interaction might limit viremia early during EBV infection. In addition, we investigate how early NK cell activation might influence the emerging adaptive immune response.

Herpesviruses are targeted by NK cells and NK cell responses are essential for the immune control of the β-Herpesvirus Cytomegalovirus. Similarly activated NK cells inhibit B cell transformation by EBV. We are interested which signals trigger NK cell recognition of EBV infected B cells and how NK cells can target EBV transformed cells. Since immune control of EBV during asymptomatic infection is entirely handled in the tonsils, we are specifically interested in the capabilities of tonsilar NK cells.

    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 and Christian Münz, "NK cell compartments and activation by dendritic cells", Journal of Immunology (2004), 172: 1333-1339.