Death Receptor-Mediated Apoptosis and Lymphocyte Homeostasis

To generate specific immunity, T and B lymphocyte clones may expand massively in response to antigenic stimulation. The expansion of antigen-specific lymphocytes allows the immune system to control pathogens and possibly neoplasia. However, in order to maintain homeostasis, a clonotypic contraction of the expanded lymphocytes is often necessary during and at the conclusion of an immune response. It has been suggested that every day, 1% of mature T cells are replenished from the thymus. ¹ In addition, given the rapid doubling time of activated lymphocytes, a single naive T cell clone can expand more than 125-fold during an immune response lasting 11 days. ^{2 , 3} The limited space of the lymphocyte compartment cannot afford unlimited expansion of activated lymphocytes. Furthermore, over-activation of lymphocytes may result in detrimental effects on host tissues and autoimmune disorders. ⁴ Therefore, in order to maintain an immune system with a diverse antigen reactivity repertoire and self-tolerance without exceeding the limited lymphoid compartment, a negative feedback control system involving lymphocyte apoptosis, termed propriocidal regulation, has evolved. ^{4 , 5}