The question of how T cells escape the thymus and enter the circulation to fight infections has finally been answered.

"These findings will be taught in textbooks down the road," Kristin Hogquist from the University of Minnesota, who was not involved in the research, wrote in an email. "This is a fascinating study," she added.

A T cell exiting the thymus Image: Courtesy of Jessica Huppi

Scientists have long wondered how T cells exit the thymus, where they mature. The thymus is threaded with both blood vessels and lymphatic vessels (containing lymphocytes suspended in a clear fluid), so researchers didn't know which exit route T cells took.

New findings published this week in Science have settled the debate: Mature T cells escape the thymus via blood vessels rather than lymphatic vessels.

Marcus Zachariah and Jason Cyster from the University of California in San Francisco investigated the question by looking at the receptor S1P1, expressed by mature T cells just before they exit the thymus. The receptor drives cells to areas, such as the blood, that are rich in S1P -- the receptor's ligand. However, it was recently shown that the S1P ligand in the blood wasn't sufficient to draw T cells out of the thymus, Yousuke Takahama, from the University of Tokushima, who wasn't involved in the research, said in an email.

The researchers observed T cells expressing the S1P1 receptor, and noticed that these cells accumulated at blood vessels of the thymus -- specifically, near pericytes, a cell type that creates a sheath around blood vessels. This suggested that the S1P ligand on these pericytes was attracting the cells to that location.

When researchers deleted the S1P expression on pericytes only, T cells were unable to exit the thymus. "This study shows that S1P-mediated thymocyte egress is not a single-step process regulated by blood-borne S1P, but a multiple-step process," regulated by both the S1P on the pericytes and in the blood, said Takahama.

M.A. Zachariah, J.G. Cyster, "Neural Crest-Derived Pericytes Promote Egress of Mature Thymocytes at the Corticomedullary Junction," Science, published online April 22, 2010, doi:10.1126/science.1188222.

Correction (April 23): An earlier version of the article described T cells as exiting the thymus via blood cells, rather than blood vessels. The passage has been corrected, The Scientist regrets the error.


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