12 Aug 2024
Revealing the blueprint of memory T cells, the key to long-term immunity
A team of researchers, led by the University of Melbourne’s Professor Laura Mackay, Laboratory Head and Theme Leader in Immunology at the Doherty Institute, has uncovered the mechanisms that govern the development of memory T cells in various parts of the body during infection.
A subset of T cells, memory T cells are specialised immune cells that ‘remember’ past infections and provide a faster and more effective response against previously encountered pathogens. Acting as the immune system’s ‘memory bank’, they are essential for ensuring long-lasting protection.
The study, published in the journal Immunity, focused on the epigenetic changes that T cells undergo to become memory T cells. Unlike genetic mutations that alter the DNA, epigenetic changes are like instructions that tell cells which genes to turn on or off, guiding their function.
The University of Melbourne’s Dr Raissa Fonseca, Research Officer in the Mackay Laboratory at the Doherty Institute and co-first author of the paper, explained that, by deciphering these epigenetic instructions, the team identified specific factors that influence memory T cells differentiation.
“We found that memory T cells develop differently depending on whether they stay in specific tissues like the liver or lungs, known as tissue-resident memory T cells (TRM), or circulate in the bloodstream, called circulating memory T cells (TCIRC),” said Dr Fonseca.
“We also discovered that TRM cells in the liver are quite distinct from those in the lungs, even though they all belong to the same T-cell family. This suggests that the environment in each organ plays a key role in shaping how these cells behave and function.”
Using advanced genetic sequencing techniques, the team mapped the epigenetic landscape of memory T cells, identifying specific genes and regulatory elements that control their development across various organs. This detailed mapping is like decoding the blueprint of T cell differentiation, providing valuable insights into how these cells adapt to their environments.
Professor Mackay, senior author of the study, highlighted the potential impact of these findings, noting that a deeper understanding of immune cell development could lead to therapies offering better protection.
“Our study’s insights into the epigenetic landscape of memory T cells reveal new factors influencing their development, paving the way for future vaccines and therapies that would target specific tissues in the body,” said Professor Mackay.
“For example, if we know what makes TRM cells in the lungs special, we could develop therapies that boost lung immunity without affecting other parts of the body. Such strategy could significantly improve immune health and overall quality of life.”
Professor Mackay emphasised the importance of collaboration in research.
“Our collaboration with the Satpathy team at Stanford University was crucial to this work. They are pioneers in epigenetics and contributed extensively to developing novel technologies in genome science,” said Professor Mackay.
“Such global partnerships are key for scientific breakthroughs and advancing human health.”
This research marks a significant step forward in our understanding of the immune system. By revealing the epigenetic mechanisms that guide the development of memory T cells, the researchers are opening the door to future therapies that could revolutionise how we treat and prevent diseases.
Peer review: Buquicchio F, Raissa F, et al. Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation. Immunity (2024). https://doi.org/10.1016/j.immuni.2024.06.014
Collaboration: Stanford University, Gladstone-UCSF Institute of Genomic Immunology.
Funding: This work was supported by the National Institutes of Health, the Australian Research Council, Howard Hughes Medical Institute and Bill & Melinda Gates Foundation, the National Health and Medical Research Council of Australia, the Sylvia and Charles Viertel Charitable Foundation, the Parker Institute for Cancer Immunotherapy, the Cancer Research Institute, the Burroughs Welcome Fund, the Pew Charitable Trust, and the UCSF, Gladstone Institutes, and the Innovative Genomics Institute at UC Berkeley.
Acknowledgements: The authors thank the University of Melbourne’s Flow Cytometry Unit and Bioresources Facility at the Doherty Institute and the Stanford Functional Genomics Facility.