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Severe combined immunodeficiency (SCID) comprises a group of disorders that are fatal owing to genetic defects that abrogate T cell development. Numerous related defects have recently been identified that allow T cell development but that compromise T cell function by affecting proximal or distal steps in intracellular signaling. These functional T cell immunodeficiencies are characterized by immune dysregulation and increased risk of malignancies, in addition to infections. The study of patients with these rare conditions, and of corresponding animal models, illustrates the importance of intracellular signaling to maintain T cell homeostasis.
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