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Strength In Numbers
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A large number of signalling motifs in the receptor complex expressed on the surface of T lymphocytes helps prevent autoimmunity, according to a study published online this week in Nature Immunology. As auto-aggressive T lymphocytes can attack healthy tissues and thereby exacerbate many autoimmune diseases, understanding the mechanisms regulating the activity of this cell type is important. Compared to other immune cells, T lymphocytes contain the highest number -- 10 -- of these signalling motifs, called ITAMs, which are required for transmission of intracellular signals. Using a complex genetic manipulation strategy, Dario Vignali and co-workers generated a panel of mice expressing various numbers of functional ITAMs on T lymphocytes. Mice with less than seven functional ITAMs suffered from lethal autoimmune disease precipitated by impaired deletion of self-reactive auto-aggressive T lymphocytes. In general, T lymphocyte development required high numbers of ITAMs, whereas mature T lymphocyte function required lower numbers of ITAMs. The molecular basis for these different ITAM 'thresholds' remains to be understood. Author contact: Dario Vignali (St. Jude Children's Research Hospital, Memphis, TN, USA) Abstract available online. (C) Nature Immunology press release.
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