New Developmental Map of Human T Cells

In a study published today in Immunity, a team of researchers generated a comprehensive roadmap for how T cells develop in the human thymus. Understanding human T-cell development is crucial for treating diseases that are caused by abnormal T-cell development and for developing highly effective immunotherapies like CAR-T.

“While most previous studies have been done in mice, our study specifically reveals a high-resolution picture of human T-cell development,” says senior author Chintan Parekh of USC. “Because of the biological differences between species, it’s critical to specifically study human T-cells in order to generate the information we need to understand human disease and to design novel immunotherapies.”

The researchers used single-cell sequencing technology to study cells isolated from human thymic tissue. During this process, they mapped the various stages of T-cell development in the human thymus, including the multitude of genes that switch on or off at each stage. They also charted the different developmental routes that the most immature cells in the thymus may take as they progress to maturity, and they discovered stages of development and patterns of gene activity unique to humans.

The findings could lead to greater insights into diseases arising from T-cell deficiencies such as immunodeficiency disorders, T-cell mediated autoimmune diseases, and leukemia. Additionally, the findings could help in the advancement of immunotherapies like CAR-T therapy, which is regarded as one of the most significant advances in cancer treatment. A greater understanding of T-cell development is also needed to advance treatments to expedite recovery of the immune system in patients who have undergone bone marrow transplantation for treatment of cancer and other diseases.

The single cell data for developing T cells is available on the National Center for Biotechnology Information (NCBI) Gene expression omnibus (GEO) database. This public genomics data repository ensures that other researchers have access to this data so that they can learn more about which genes regulate T-cell development and then use that knowledge to design new immunotherapies against T-cell diseases.