Origins of immune system mapped ‘opening doors for immunotherapies’

The origins of the immune system have been mapped, opening up new doors for cancer immunotherapies, a new study suggests.

Researchers mapped thymus tissue through the human lifespan to understand how it develops and makes vital immune cells called T cells.

They say this information could help researchers generate an artificial thymus and engineer improved therapeutic T cells.

The scientists say the human thymus atlas has revealed new cell types and identified signals that tell immature immune cells how to develop into T cells.

It could help them understand diseases that affect T cell development such as severe combined immunodeficiency (SCID).

The research adds to the Human Cell Atlas initiative which is creating a Google map of the entire human body.

Dr Jongeun Park, the first author on the study from the Wellcome Sanger Institute, said: “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.

“This openly available resource will allow researchers worldwide to understand how the immune system develops to protect our body.”

The thymus gland is located in the chest and produces T cells – key white blood cells that fight infection and disease.

These T cells then leave the thymus to enter the blood and other parts of the body, seeking out and destroying invading bacteria and viruses, and also recognise cancer cells and kill them.

Problems in thymus development causes can result in severe immune deficiencies, and can affect T cell regulation resulting in autoimmune diseases such as Type 1 diabetes.

While mature T cells have been well studied, the development of the human thymus and T cells within it is not fully understood.

Professor Muzlifah Haniffa, a senior author of the study from Newcastle University and senior clinical fellow at the Wellcome Sanger Institute, 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 tumours.”

Researchers analysed around 200,000 individual cells from the developing thymus, and child and adult thymus tissue.

They looked at which genes were active in each individual cell to identify the cells, discovering new cell types, and used those genes as tags to map each cell to its exact location in the thymus.

The study by researchers at the Wellcome Sanger Institute, Newcastle University and Ghent University, is published in the Science journal.