How T cells kill cancer cells at the cytotoxic immune synapse

How T cells kill cancer cells at the cytotoxic immune synapse

A new report published in The Journal of Immunology identifies the spatiotemporal events, and the role of calcium flux and the degranulation of cytotoxic lymphocytes in the process of rapid formation by these cells of immune synapses and the killing of their target cells.

The cytotoxic lymphocytes (CLs) destroy virus-infected and malignant cells via an effective engagement with their target cells and a process entitled ‘immunological synapse’. Importantly, the ‘immune synapses’ are crucial factor for the killing of virus-infected or malignant cells. Immune synapses’ formation triggers exocytosis of lytic granules containing the effector molecules perforin and granzymes, into the synaptic cleft, in a process known as degranulation.

In some cases, the nano-scale gap of the immunological synapse take place between T cells and antigen presenting cells, and this bears a striking similarity to the classical synapse of the central or peripheral nervous system.

In the Journal of Immunology study the researchers from East Melbourne, Victoria, Australia have used a novel live cell microscopy technique to visualize the engagement of primary human and mouse T cytotoxic lymphocytes with their targets and the subsequent delivery of the lethal hit.

”For the first time we have got this marker of the delivery of the lethal hit” said immunologist Misty Jenkins from the Peter MacCallum Cancer Centre.

Using this technique, the researchers have uncovered two critical features of the lethal hit: a defined focal delivery and rapid target cell membrane resealing.

The study suggests, and as Bridie Smith described this phenomenon – it takes no more than 100 seconds for the body’s immune cells to identify and kill a cancer cell. And for the first time, researchers have gained an insight into how the body’s immune system, and particularly T-cells, react to diseased or virus-infected cells.

This is perhaps the first study showing that perforin pore delivery is unidirectional, occurring exclusively on the target cell membrane, but sparing the killer cell.

Source: J Immunol. 2013 Sep 1;191(5):2328-34. doi: 10.4049/jimmunol.1301205. Epub 2013 Jul 24.
Read more: The Journal of Immunology
See also: theage.com.au

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