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New research published in Cell Reports by the Dustin Group has discovered a new way for immune cells to relay information about infection or genetic mutations through dynamic, yet durable cell contacts before deciding how to respond.

Time lapse shown as a montage (time increasing from left to right & then through rows with interval of 2.5 minutes), of a human T cell engaging with a printed spot displaying messenger-associated signal. The cell moves around continuously but always pinned down, thus ensuring durable and continuous interaction. Note: raw images have been superimposed and smoothed for illustration.

T cells in the immune system need to have information about infection or mutation (such as cancer) presented to them through physical contact with messenger cells, including dendritic cells. These physical conversations must go on for hours to reach a conclusion – an appropriate, or sometimes pathological, immune response.  

The paradigm for this communication is a prolonged one-to-one interaction referred to as an immunological synapse after the stable communication platform also used in the nervous system.  

The new research revealed that the majority of human T cells intrinsically use a more flexible mode of interaction with messenger cells. In which, the T cells not only keep a “foot” on one messenger with interesting information to share, but continually pivot and probe for contacts with other potential messengers that may reinforce the same message or add new information, opening the possibility of local networking to make a decision.  

Importantly, this flexibility to gather information from multiple messengers in no way impairs the ability of the T cell to stay in contact with the first messenger cell, if no other messengers come within reach of the pivoting T cell. The researchers expect that the ability of T cells to listen to one messenger or incorporate information from dozens of messengers (if available) leads to high sensitivity and robust decision making.  

This discovery was enabled by developing a model system in which the messenger cells were replaced by similar sized, printed spots of key messenger associated proteins on a surface that live human T cells explored in a lab setting while being observed with a microscope.  Quantitative observations of these in lab explorations, correlated with historical data from observations in live tissues, provided insights into events that take place in the more difficult to access tissue spaces in the human body.

Commenting on the research, Professor Michael Dustin said:

“We are very excited about this research. It is the first analysis of how different human T cells subsets behave when presented with their natural targets. It also develops a new analysis for identifying cells that are forming stable or motile junctions when faced with these signals. It is the first new approach to this problem in 15 years.”

You can read more about this research in Cell Reports:

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