For the first time, embryonic stem cells were "taught" how to become T lymphocytes without the need for an embryo or a thymus. In the April issue of Nature Immunology, Juan-Carlos Zúñiga-Pflücker and colleagues from Toronto generated fully functional T cells from mouse embryonic stem cells using defined growth conditions for differentiating the embryonic stem cells. This method could aid efforts to grow large quantities of T cells for immunotherapeutics.
Embryonic stem cells are totipotent, meaning that they have the potential to become any cell found in the body. However, a specific sequence of cues is needed to specify the type of cell into which they eventually develop. Zúñiga-Pflücker identified the sequence that gives rise to T lymphocytes. Mouse embryonic stem cells were cultured on a layer of "support" cells that express a membrane molecule called Delta-like ligand 1 (DL1), in addition to other nutrients required for survival of the young T cells. DL1 interacts with a protein called Notch on the surface of developing T lineage cells and sends signals that reinforce development to fully fledged T cells. When introduced into a T cell-deficient mouse, these cells were able to confer immune responses to virus infection, suggesting that they are fully functional. This finding may bring reconstitution of T cell functions lost in cancer or AIDS infection one step closer.
Juan Carlos Zúñiga-Pflücker
University of Toronto
Tel: +1 416 480 6112
Additional contact for comment on paper:
Ellen V. Rothenberg
Tel: +1 626 395 4992
Also available online.
(C) Nature Immunology press release.
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