drj writes "Why did the lymphocyte leave the lymphoid organ? A chemical gradient was long suspected and now some details have been identified. Matloubian et al. found very few lymphocytes in the blood of mice with lymphocytes that are deficient in one particular receptor for sphingosine-1-phosphate (S1P), called S1P1. They show that developing S1P1-deficient thymocytes remain in the thymus and B cells remain in peripheral lymphoid organs, though there is only a mild alteration in the the subpopulations within these organs. Normal thymocytes but not deficient thymocytes move in response to a S1P gradient. Antigen stimulated T cells transiently reduce S1P1 expression, which is mostly restored within days, suggesting a molecular basis for transient retention in lymphoid organs. An immunosuppressant drug currently in clinical trials, FTY720, binds S1P1, leading to receptor downregulation and reduced migration. The data strongly support a compelling model, albeit one with many details yet to be determined."
M. Matloubian et al. Nature 427:355-360. January 22, 2004
Wednesday, September 6, 2006
Lymphocyte migration triggered by sphingosine-1-phosphate
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gradient?
They show that S1P is chemoattractive with 10 nM causing ~2% of mature thymocytes to migrate and 100 nM causing ~4% to migrate (Fig. 3, baseline ~0.2% migration). Without a gradient, S1P caused little or no cell migration (p. 357). They cite papers stating that the constitutive concentration of S1P levels blood is high (100-400 nM in plasma, p.358). It will be important to see whether the inter-thymic levels of S1P are lower than the plasma levels, as required to form the proposed chemoattractive gradient.
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