The first cell atlas of the human thymus gland has been mapped using scRNA-seq and it could lead to new immune therapies to treat cancer and autoimmune disease. The thymus makes T cells, and these are currently being used to treat B-cell lymphoma and leukemia. CAR-T—chimeric antigen receptor T-cell—therapy is specifically developed for each individual patient and involves reprogramming the patient’s own immune system cells which are then used to target their cancer.
A major drawback to such treatments has been creating the right subtype of T cells. While mature T cells have been well studied, the development of the human thymus and T cells within it is not fully understood. Researchers from the Wellcome Sanger Institute, Newcastle University and Ghent University, Belgium, have now mapped thymus tissue throughout the human lifespan.
Their report was published today (Feb. 20) in Science, and has revealed new cell types and identified signals that tell immature immune cells how to develop into T cells.
This data will be widely shared, and alsoadds to the Human Cell Atlas initiative which is a comprehensive collection of maps that will describe and define the entire cellular basis of health and disease.
“We have produced a first human thymus cell atlas to understand what is happening in the healthy thymus across our lifespan, from development to adulthood, and how it provides the ideal environment to support the formation of T cells,” said Jongeun Park, PhD, the first author on the study and a postdoctoral fellow at Wellcome Sanger Institute. “This openly available resource will allow researchers worldwide to understand how the immune system develops to protect our body.”
They write “We applied scRNA-seq to generate acomprehensive transcriptomic profile of thediverse cell populations present in the embryonic, fetal, pediatric, and adult stages of thehuman thymus, and we combined this withdetailed TCR repertoire analysis to reconstructthe T cell differentiation process.” They identified and located in situ novel CD8αα+ T-cell populations, thymic fibroblast subtypes and activated dendritic cell (aDC) states. In addition, they “Reveal a bias in TCR recombination and selection, which is attributed to genomic position and suggests later commitment of the CD8+ T-cell lineage.”
Muzlifah Haniffa, PhD, a senior author of the study said: “With this thymus cell atlas, we are unravelling the cellular signals of the developing thymus, and revealing which genes need to be switched on to convert early immune precursor cells into specific T cells. This is really exciting as in the future this atlas could be used as a reference map to engineer T cells outside the body with exactly the right properties to attack and kill a specific cancer – creating tailored treatments for tumors.” Haniffa is also a professor at Newcastle University and senior clinical fellow at the Wellcome Sanger Institute,
“We now have a very detailed understanding of how T cells form in healthy tissue. We have been able to identify a similar population of precursor cells in the developing thymus and liver, and we believe that these precursors are important for initiating T cell development in the fetus, and for the establishment of a fully competent thymus organ. This is helping us put jigsaw pieces together to get a bigger picture of how immunity develops,” added Tom Taghon, PhD, a senior author of the study and professor from Ghent University, Belgium.