While much research focuses on T and B cells entering lymphoid organs, Jason Cyster says he's more curious about how they get out. He and colleagues at the University of California San Francisco found a clue to lymphocyte escape, both from the thymus and secondary lymphoid organs, in an immunosuppressant drug, FTY720. The drug sequesters T and B cells in lymphoid organs and is known to interact with sphingosine-1-phosphate (S1P) receptors.
Cyster's team found that in knockout mice lacking S1P receptor 1 (S1P1), mature T cells can't exit the thymus and B cells recirculate poorly.1 While S1P1 is downregulated during normal T-cell maturation and sequestration in lymphoid organs, they found, responsiveness to the receptor is upregulated prior to egress. Lymphocytes require the receptor to recirculate in the periphery and demonstrate a chemotactic response to S1P, which is found in high levels in the blood.
It was surprising to find lymphocytes ...
