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.
Dario Vignali (St. Jude Children's Research Hospital, Memphis, TN, USA)
Abstract available online.
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza