ABSTRACT
National Institute of Allergy and Infectious Disease, National Institutes of Health Building 10 CRC, Room 5W-3940, 10 Center Drive, Bethesda, MD 20892, USA
E-mail: Jeremiah.Davis@nih.gov 2Human Immunological Diseases Unit, Laboratory of Host Defenses,
National Institute of Allergy and Infectious Disease, National Institutes of Health Building 10 CRC, Room 5W-3940, 10 Center Drive, Bethesda, MD 20892, USA
E-mail: hsu@niaid.nih.gov
Research within the last two decades has revealed a complex and critical system of programmed cell death (PCD) in immune cells that helps maintain immunological homeostasis. Our understanding of apoptosis in normal immune function has been greatly informed by the study of rare patient phenotypes and the animal models they resemble (Sneller et al. 1992). Genetic defects uncovered in patients with Autoimmune Lymphoproliferative Syndrome (ALPS) or other conditions of lymphocyte accumulation and autoimmunity illustrate the importance of cell extrinsic apoptosis signals communicated by death receptors (DR), as well as cell intrinsic signals that function through mitochondrial pathways. Patient studies continue to yield new insights. Connections between traditional PCD components like caspase-8 and known growth and proliferation signals such as NF-κB have recently emerged (Su et al. 2005). Many clinical features remain unexplained, including the variable clinical penetrance seen in ALPS and the unpredictable manifestation of autoimmune disease. Solving these puzzles may allow us to manipulate apoptotic pathways to treat a wide range of diseases.
