Serpins in T Lymphocyte Immunity and Blood Development

T lymphocytes are required for cell-mediated immunity but also give rise to immunological diseases such as autoimmunity and transplantation rejection. Intracellular serine protease inhibitors (serpinsIC) regulate the activity of key of proteases that control T lymphocyte function and development. An emerging view of serpinsIC is that they are important promoters of cellular viability through their inhibition of executioner proteases. This will be discussed in the context of the T lymphocyte survival during effector responses and the development and persistence of long-lived memory T cells. The potent anti-apoptotic properties of serpins can also work against adaptive cell immunity by protecting viruses and tumors from eradication by cytotoxic T cells (CTL). Recent insights from knockout mouse models demonstrate that these serpins also are required for hematological progenitor cells and so are critical for the development of lineages other than T lymphocytes. Given the emerging role of serpins in multiple aspects of lymphocyte immunity and blood development, this chapter will examine new immunotherapeutic approaches based directly on serpins or on knowledge gained from identifying their physiologically relevant protease targets.