Welcome to the next installment of our regular update where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past few weeks.
Gamma-delta T cells revealed to be the one-stop shop for a speedy yet specific immune response
The immune system can broadly be divided into innate and adaptive ‘arms’. The innate immune system detects pathogens and abnormal cells – such as those infected with viruses or cancer cells - and mounts a fast, inflammatory response. The adaptive immune system responds to molecular cues and ‘danger signals’ from the innate immune system before mounting a specific and long-lived response against the pathogen at hand. Gamma-delta T cells are a type of immune cell found in areas such as the gut and skin. Due to their ability to perform fast, innate-like tissue surveillance while having some – if limited – specificity to what they can detect, gamma-delta T cells are thought to sit somewhere in the middle of these two arms.
A study published recently in Nature Immunology has unveiled an exciting function of gamma-delta T cells that challenges the notion of the immune system existing in two separate arms. Research teams at the Francis Crick Institute and King’s College London, from BSI member and study leader Professor Adrian Hayday, showed that gamma-delta T cells can perform both innate and adaptive functions by using a single molecule found on their surface. Using this molecule, gamma-delta T cells use a two-pronged approach to check a cell’s abnormality – an innate function – and then mount a specific attack, as seen in the adaptive response, without having to rely on authorisation from other immune signals.
Describing the findings, Professor Hayday said, “These maverick immune cells act as judge, jury and executioner, identifying and killing potentially dangerous cells in the body. This discovery was a huge surprise. It fundamentally changes our understanding of how the immune system makes critical judgment calls about when to act and when to hold back. This could open up exciting possibilities for treating disease.”
Read the press release here.
Read the full article here: Melandri D. et al. 2018 Nature Immunology DOI: https://doi.org/10.1038/s41590-018-0253-5
Pre-natal negotiations: Foetal cells initiate peace talks with the maternal immune system
During the early stages of pregnancy, the lining of the uterus transforms into the decidua. The foetal placenta implants into the decidua, allowing for maternal and foetal cells to intermingle and communicate. The immune system is trained to recognise and attack ‘non-self’ cells such as those received from transplant or, indeed, foetal cells. During pregnancy however, the mother’s immune system is modified to ensure it doesn’t attack the foetus and allow the pregnancy to progress successfully. Until now the cellular mechanisms behind this modification have remained unclear.
A study published this month in Nature investigated which genes are switched on and off in around 70,000 cells from the placenta, decidua and maternal blood. As well as elucidating the cellular organisation of the implantation site of the foetal placenta to the decidua, the team from Newcastle University and the Wellcome Sanger Institute showed that foetal cells present at this site communicated with maternal cells through the expression of regulatory genes to prevent potentially harmful maternal immune responses, protecting against complications such as miscarriage and stillbirth. Furthermore, the team discussed how these findings had implications in cancer therapy, as tumour cells are known to use similar mechanisms to evade the immune system.
Speaking on the work, BSI member and joint leader of the study Professor Muzlifah Haniffa said, “Our single cell study has shown us the exact cellular composition of the decidua and placenta for the first time, and how the cells from the developing placenta and uterus communicate. This has huge implications for understanding what happens in a normal pregnancy, and for studying what can go wrong during conditions such as pre-eclampsia and miscarriage.”
Read the press release here.
Read the full article here: Vento-Tormo R. et al. 2018 Nature DOI: https://doi.org/10.1038/s41586-018-0698-6
Teaching tolerance with peanut powder gives new hope to allergy sufferers
Peanut allergies arise as a result of the immune system mounting an inappropriate response to proteins found within peanuts. Reactions can range from mild itching and redness to potentially life-threatening anaphylaxis, whereby tissues such as the tongue and throat swell to the point where breathing is restricted. Although symptoms of an allergic reaction can, in some cases, be alleviated with anti-histamines, there are currently no permanent treatment options.
In a clinical trial carried out by researchers and doctors at King’s College London (KCL) and the Evelina London Children’s Hospital, participating children and teenagers who could not tolerate one tenth of a peanut were given gradually increasing amounts of peanut protein over the course of six months. By the end of the study, around two thirds of the participants could tolerate two whole peanuts, meaning that people with severe peanut allergies can be protected from life-threatening anaphylactic reactions.
Of the study, published in the New England Journal of Medicine, Professor George du Toit, Honorary Senior Lecturer at KCL and paediatric allergy consultant at Evelina London said, “The results of this ground-breaking study are very promising and suggest that we will be able to protect children who are allergic to peanuts from having a severe reaction after accidental exposure.
“This is extremely good news as the number of children being diagnosed with peanut allergy in the UK has more than doubled over the past two decades. Peanut allergy is extremely difficult to manage for children and their families, as they have to follow a strict peanut free diet. Families live in fear of accidental exposure as allergic reactions can be very severe and can even lead to death. These findings could lead to a significant shift in our management of peanut allergy as we now have data from a large randomised trial that oral immunotherapy worked for most of the participants.”
Read the press release here.
Read the full article here: Vickery B. P. et al. 2018 The New England Journal of Medicine DOI: https://doi.org/10.1056/NEJMoa1812856