How does the immune system self-regulate?
Researchers identify a key molecule controlling two waves of Regulatory T cells, which work to meditate killer T cells and protect healthy tissue surrounding infections.
Regulatory T cells control the immune reaction from killer cells to ensure healthy tissue surrounding an infection is protected. Researchers from La Jolla Institute for Immunology (CA, USA) have been studying these regulatory T cells – named Tregs – and discovered not only the mechanism of protection but that there are two heterogenous Tregs that perform specific roles depending on the stage of infection.
The immune system, through impressive regulatory pathways, gathers a team of cells and cytokines to battle unwanted pathogens in the body. Understanding the detail of these pathways and the exact role of each player is key to developing more tools to fight infections and disease. Until recently, our understanding of regulatory T cells and their mechanisms to protect healthy tissue has been limited but this knowledge could hold the key to fighting chronic inflammation and autoimmunity.
The team, led by Stephen Schoenberger, used T-cell receptor sequencing technology to analyze Treg cell response to listeria infection. Interestingly they discovered two waves of Tregs, which appeared at the initial and final phases of infection to control immune response. While both groups behaved differently the key molecule in the action of both T-cell groups was Adenosine – a basic building block of DNA. Adenosine is normally stored deep within cells in the DNA. However, tiny fragments of DNA are released when cells are ripped apart by invading pathogens and immune system cells.
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When the immune system recognizes an external pathogen two key T cells arrive at the scene – CD4+ T cells known as helper cells and CD8+ T cells known as killer cells. The first group of Treg cells evolve rapidly from CD4+ T to block uncontrolled upregulation of killer cells and protect the healthy tissue surrounding the infection. The researchers found that adenosine acts as a warning to Treg cells, which then, attract molecules to bind to receptors in killer cells slowing their functionality. This acts to control the reaction of the killer cells and toe the line between removing the full infection and damaging healthy tissues further.
The study also found the second wave of cells arrived around 7 days after infection when most of the pathogenetic cells had been killed. The later wave of Treg cells respond to adenosine by directly producing a molecule called cAMP, which is a potent regulatory molecule that binds to the killer cells inhibiting functionality.
“This work shows how the immune system has devised this remarkable way to rapidly protect the host from acute inflammation,” commented Schoenberger.
The team hopes to continue to increase their knowledge of Treg cells, particularly where they reside in the body and how they interact with other cells of the immune system. Further understanding of how these cells operate and triggers of regulation could advance how we treat immune system failures such as chronic inflammation and autoimmune diseases.
