| Natural killer cells are lymphocytes important for fighting viral infections and cancerous cells. NK cells also link innate and adaptive immunity by setting up an environment that recruits and guides adaptive immune responses. Thus, it is important and prescient to understand NK cell recognition and activation.; Human NKp30 is a unique Ig-like stimulatory natural cytotoxicity receptor implicated in tumor and viral immunity, and it is the major NK receptor to mediate interactions with dendritic cells. To expand our comprehension of NKp30, we have identified, cloned and characterized a novel NK activation receptor, rat NKp30 (rNKp30). Rat NKp30 is homologous to human NKp30 (hNKp30) and exists as a single copy gene. We show that rNKp30 RNA is expressed in normal rat spleen, lymph node, and lung tissues. RT-PCR and flow cytometric analysis using anti-rNKp30 monoclonal antibodies confirmed that NK cells express rNKp30. Additionally, we show that rNKp30 is not restricted to NK cells as surface protein expression is also found on monocytes, B cells, granulocytes, and a small subset of NKT cells. Focusing on rNKp30 in NK cells, we found that rNKp30 is a transmembrane glycoprotein that is expressed on a subset of NK cells in the spleen and blood and to a lesser extent in the liver. We demonstrate that rat NKp30 is a functional activation receptor on NK cells that mediates robust IFNgamma production. Using a rat allogeneic orthotopic liver transplant model, we examined NKp30 during an immune response in vivo. Our data demonstrate that in the peripheral blood, the proportion of rNKp30+ NK cells to the whole NK cell population increases after allo-activation, simultaneous to when peak IFNgamma levels are detected.; In addition to finding a novel rat NK receptor and contributing to our understanding of NK cell biology, we have expanded the role of NKp30 beyond NK cells. We also show that the rat can be used as a model to investigate the role of NKp30 in the immune response in vivo. Therapeutic implications suggest that successful manipulations of NKp30 to inhibit or harness its power may lead to favorable immunological outcomes. |
