Cytotoxic T Lymphocytes: Target Cell Killing: Cellular Parameters

From the moment lymphocyte-mediated cytotoxicity was first defined, there were two major questions driving research in the field that its discovery engendered. The first was to understand how CTL (and, as would be appreciated later, the T-helper cells that promote the functional maturation of CTL) recognize the cells with which they interact, both during the sensitization phase of the CTL reaction, when the decision between self and non-self must be made, and later, when the CTL must interact with and kill non-self or compromised-self cells. In other words, what was the chemical nature of the T-cell receptor (and associated molecules) for antigen? The second problem, specific to the field of lymphocytotoxicity, concerned the nature of the lytic mechanism by which CTL, once sensitized, were able to destroy specifically recognized target cells. Interestingly, both of these problems began to be resolved at almost the same time, in the early 1980s, making this an extraordinarily exciting time in CTL immunology. But while the nature of the T-cell receptor was determined in considerable detail in just under two years, a full appreciation of the mechanism – mechanisms, as it turned out – used by CTL to destroy target cells would take a full decade and is still incomplete.