Regulation of T-cell apoptosis by reactive oxygen species.
To ensure that a constant number of T cells are preserved in the peripheral lymphoid organs, the production and proliferation of T cells must be balanced out by their death. Newly generated T cells exit the thymus and are maintained as resting T cells. Transient disruption of homeostasis occurs when naïve T cells undergo antigen-induced expansion, a process involving intracellular signaling events that lead to T cell proliferation, acquisition of effector functions, and, ultimately, either apoptosis or differentiation into long-lived memory cells. The last decision point (death vs. differentiation) is a crucial one: it resets lymphoid homeostasis, promotes protective immunity, and limits autoimmunity. Despite its importance, relatively little is known about the molecular mechanisms involved in this cell fate decision. Although multiple mechanisms are likely involved, recent data suggest an underlying regulatory role for reactive oxygen species in controlling the susceptibility of T cells to apoptosis. This review focuses on recent advances in our understanding of how reactive oxygen species modulate T-cell apoptosis.
Hildeman
David A
DA
Division of Immunobiology, Children's Hospital Medical Center Cincinnati, OH 45229, USA. David.Hilderman@chmcc.org
D000818:Animals; D000941:Antigens / Q000737:chemistry; D017209:Apoptosis; D049109:Cell Proliferation; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000473:pathology*
D000941:Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species