20 April 2020

British researchers have unveiled new insights into how T cells have a range of responses to immune signals, which could shed light on the involvement of the immune system in autoimmune diseases and cancer.

A study, published last week in Nature Communications, looked at blood samples to view the way memory T cells form and respond to cytokines and other immune signals. T cells donated by healthy volunteers were analysed to see which genes were switched on, both in bulk populations and in individual T cells.

The T cells were then exposed to different immune molecules – cytokines – to mimic how the cells change during the immune response in the body.

The work highlighted a continuum of T cell development, in which they responded faster to specific cytokines depending how often they had previously encountered it. They also revealed that T cell subsets were less specialised than previously thought, finding that even highly exposed memory T cells could be triggered by other, new immune signals.

Eddie Cano-Gamez from the Wellcome Sanger Institute in Cambridge, one of the co-lead authors of the study, believes the discovery of this “spectrum of responsiveness” could indicate what goes wrong in immune diseases and help guide research into drug targets for such diseases.

He said: “Previously people thought that memory T cells had two stages of development, but we discovered there is a whole spectrum of memory experience.

“From naive T cells that have never been activated, to highly trained memory T cells which can react quickly, and many intermediate T cells in between. This spectrum not only affects how fast a cell can respond, but even what signals it can respond to.”

Senior author Dr Gosia Trynka added: “We were surprised to see how flexible and complex the memory T cells’ response could be. Understanding this varied T cell response could help us understand our response to infections such as viruses, and also give clues to what is going wrong in immune diseases such as asthma and type 1 diabetes.”

Source: Cano-Gamez E, Soskic B, Roumeliotis TI, So E, Smyth DJ, Baldrighi M, Willé D, Nakic N, Esparza-Gordillo J, Larminie CGC, Bronson PG, Tough DF, Rowan WC, Choudhary JS, Trynka G (2020) “Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines”, Nature Communications, doi: 10.1038/s41467-020-15543-y


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