Stability of a diverse immunological memory is determined by T cell population dynamics

The correlation between properties of the T cell memory pool and the two regulatory mechanisms of cell death (apoptosis) and memory entry (differentiation) is investigated mathematically. Apoptosis of T cells occurs at the end of an immune response, removing unwanted activated T cells. T cells escaping apoptosis enter the memory pool composed of T cells specific for previously encountered antigens. We find that the relative efficiencies of these two pathways determine the clonal distribution and the long-term stability of the memory pool by regulating the number of new entries. The main result presented in this paper is that immunological memory of previously encountered pathogens cannot be erased by either severe or repeat infections with a particular pathogen (the diversity of the memory pool is ensured) only if apoptosis and/or memory differentiation are regulated by population dependent processes. Furthermore, vaccination properties are improved significantly by population dependent mechanisms and our mathematical analysis reveals that the T cell population must communicate with other parts of the immune system to ensure optimal performance of immunological memory. (C) 2001 Society for Mathematical Biology