Real time microscopy tracks the course of developing T cells

In the service of optimum immune defense, the mammalian adaptive immune system churns out billions of T cells a day. Precursor T cells originate in the bone marrow and migrate to the thymus, where the immune mettle of the developing T cell, now called a thymocyte, is tested by a selection process that only about 1% will survive. In their new study published in the open-access journal PLoS Biology, Ellen Robey and her group follow T cells in real time in living tissue to shed light on this critical test of immune fitness.

Immature thymocytes inhabit the outer layer of the thymus, called the cortex, while more mature thymocytes are found in the central medulla. How a thymocyte reacts to other cells as it wends its way through the thymus determines whether it matures into a helper or killer T cell, or undergoes programmed cell death. The signaling cues that guide this process remain obscure.

In their study, Robey and her colleagues took advantage of a recent technological innovation called two-photon microscopy to visualize the migration of thymocytes in intact thymuses extracted from mice. They found that after cells undergo positive selection - which seals their fate as either helper T or killer T cells - they make a beeline for the thymus interior (called the medulla).

Though it's been known that positively selected thymocytes migrate to the medulla, this study shows that migration follows a clear directional course, possibly guided by long-range signaling cues. Homing in on the source of these long-range signaling cues and characterizing the migratory patterns of these cells will go a long way toward understanding how the major components of immunity acquire their defensive chops.

Citation: Witt CM, Raychaudhuri S, Schaefer, Chakraborty AK, Robey EA (2005) Directed migration of positively selected thymocytes visualized in real time. PLoS Biol 3(6): e160.

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