Kinetics of cell-mediated cytotoxicity: Stochastic and deterministic multistage models

One of the body's major defenses against viral diseases and tumors is the killing of abnormal cells by host defense cells, such as T lymphocytes. The mechanism by which killing is accomplished is unknown. Here we develop both stochastic and deterministic models for the kinetics of killing in aggregates which contain a single lymphocyte and multiple target cells (LT_n conjugates), as might be seen early in an immune response, and in aggregates containing multiple lymphocytes and a single target cell (L_nT conjugates), which is characteristic of the late phase of a successful immune response. Comparing our models with data, we rule out the possibility of certain classes of lytic mechanisms and draw attention to the characteristics of likely mechanisms. Our stochastic model can be viewed as a specialized application of queueing theory to cell biology. For certain choices of arrival-time and service-time distributions, we find an exact correspondence between our stochastic and deterministic models.