MODELING T-CELL MEMORY

A new mathematical model of T helper-cell activation and proliferation is investigated. The model incorporates recent data and theories abou t memory T cells. It accounts for the interacting population dynamics of resting, activated and memory T helper cells, interleukin 2 and rep licating antigen, and is able to mimic a broad range of available data on T helper-cell proliferation and the effects of interleukin 2. The model is tested against existing in vitro data. It is then used to mak e novel interpretations of some recent experimental findings and predi ctions about the outcome of further experiments. Predictions made by t he model fall into three groups concerning persistent infections, cell transfer experiments, and the return of memory cells to the resting s tate. The model predicts the existence of a group of persistent infect ions which result from slow growing replicating antigens and can be cl eared by a boosting dose of antigen. A threshold is derived for the nu mber of cells that must be transferred in order to transfer long-term immune memory from one animal to another. The existence of such a thre shold implies that when small numbers of cells are transferred, or the transferred cells are in the resting state, cells alone cannot confer long-term memory on a recipient animal. However, if enough activated cells are transferred, it is possible to transfer long-term immune mem ory without antigen. The biological significance of a pathway whereby memory cells can lose their phenotypic;and functional differences to r eturn to the resting state is studied. A threshold concerning the rate of that return is derived; and it is only if the rate of return is ab ove that threshold is there any impact on the. response to a replicati ng antigen.