Proliferation versus Contraction of Immune Cells, the Non-Apoptotic Role of Caspase 8 In Immune Homeostasis

Upon antigen stimulation, immune-responsive cells, particularly antigen-specific T-cells, are activated and begin to proliferate, which is a requirement for the immune system to counteract effectively pathogen invasion and other pathogenic disturbances. For a long period of time, the major interests of immunological researchers have been focused on how to promote immune responses against given antigens; specifically, to make effective vaccines. Research has now shown that in the immune system, all mature T cells are positively selected through recognition of self-antigens in the context of MHC (major histocompatibility complex). Thus, unrestricted expansion of any specific population of T cells may not always be a benefit for a host; rather, autoimmunity and other toxic reactions can occur in certain circumstances [1]. Therefore, it has been gradually appreciated that in a healthy and balanced immune system, the proliferation and contraction of immune cells during an immune response are equally important. Following the proliferation and accomplishment of effector functions against antigen-induced disturbances, the expanded T-cells need to be removed, bringing the immune system to a new homeostatic status. Early studies on T-cell apoptosis have proposed a hypothesis that programmed death (PCD) of activated T cells serves as a suicidal retrenchment mechanism which counterposes the proliferation of T cells in a clonally specific manner [2, 3]. Since then, substantial evidence has uncovered malfunctions of lymphocyte apoptosis, one of the major mechanisms for PCD, that directly impair immune contraction, causing overpopulation of T cells and other immune cells. These have led to the discoveries of genetic defects of CD95 and CD95 ligand accountable for the lymphoproliferative ( lpr ) disorder and the general lymphoproliferative disease ( gld ) in mice [4, 5]; and the autoimmune lymphoproliferative syndrome (ALPS) in humans [6–8, 41]. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.