The existence of a unique kind of immune cell - the killer lymphocyte - which destroys other cells in a highly specific manner, has fascinated immunologists for over half a century. How do these cells, which have lived in communal harmony with their host, decide that some of their cohabitants must die? And how do they kill them?

The definition of killer lymphocytes came from discovery of their roles in a wide range of in vivo phenomena such as transplant rejection, virus infection and its related immunopathologies, and anti-tumor responses. Yet for the most part almost everything we know about these cells has come from studying them in vitro. They have yielded their secrets slowly and reluctantly. To understand fully how they work, geneticists and immunologists had to unravel the major histocompatibility systems of vertebrates, a long and torturous road that provided some of the darkest hours of immunology. The search for antigen-sensing receptors on both T cells and NK cells was scarcely less frustrating. And the holy grail of cell-mediated cytotoxicity Ð defining the mechanism by which killer cells take down their adversaries Ð sorely tested the ingenuity, patience and mutual good will of laboratories around the world.

These questions have now largely been answered. But do we really understand these cells? We can tame them to a large degree in transplant rejection. It may yet turn out that we can harness their immunotherapeutic potential in treating viral and malignant disease. The pivotal role of CTL induction has become part and parcel of many vaccination schemes. But it has become less clear with time that the dramatic destruction of cells wrought by killer cells in vitro represents their principal function in vivo.

In writing this book we had several goals in mind. First, we wanted to provide a definitive resource for the subject of cell-mediated cytotoxicity - killer lymphocytes. We felt it would be useful to have a single volume that traces the history of this field, telling its story in terms of key experiments and ideas that have shaped research into the function and biological meaning of cells that kill other cells. At the same time, we wanted to integrate, where possible, the major themes coursing through this subject in its fifty or so year history. And finally, we felt it is time to assess the evidence for and against a role of killer lymphocytes in vivo.

Having worked actively in the field for over thirty years, we were still surprised by how extensive it has become. We estimate - admittedly somewhat loosely - that well over 100,000 papers have been published on various aspects of cell-mediated cytotoxicity (CMC) since it began. Our goal could not possibly be to cover all of this information. We have tried to identify those papers that were key to the origin of each of the many themes in CMC, and then to identify key recent reviews that allow anyone interested in a given sub-topic to work their way back through the existing literature as suits their needs. We have done our best to keep the number of papers cited to a minimum, consistent with that goal. We apologize in advance to our many friends and colleagues whose many excellent and important papers have not been cited here.