A new study led by the Children’s Hospital of Philadelphia (CHOP) has revealed that a regulatory class of human T cells comes from two different origins, one that relates to protective immunity and the other to autoimmunity.
The results of the study, published in Science Immunology, can help develop new therapies for autoimmune diseases that selectively target the immune system, according to Children’s Hospital of Philadelphia.
Children’s Hospital of Philadelphia allergy and immunology division attending physician Neil Romberg said: “When it comes to autoimmunity, the prevailing wisdom has been that the only way to stop inflammation is to suppress the immune system broadly, making patients more susceptible to infection.
“However, that is only true if all T cells come from the same place. What this study shows is that there are two different T cell lineages, which means you might be able to have your cake and eat it too – suppressing inflammation due to autoimmunity while allowing T cells that fight infection to thrive.”
In the study, the team of researchers used a combination of computational, in vitro, and in vivo techniques for describing the origins, functions, and positions of T follicular regulatory (Tfr) cells within Germinal centres (GCs).
The team assessed tonsils that had been removed from healthy donor patients. Tonsils and other secondary lymphoid tissues house the GCs.
With the help of an interlocking suite of single cell technologies, the researchers found that there is a Tfr cell subpopulation that is induced by T follicular helper (Tfh) cells, which they termed as iTfrs.
Additionally, they found another subpopulation of Tfr cells which were derived naturally from Tregs, a subpopulation of T cells. The study called it nTfrs.
This showed that there are two developmental trajectories, which are Treg-to-nTfr and Tfh-to-iTfr, Children’s Hospital of Philadelphia said.
Furthermore, the researchers investigated if there is any difference in how the two regulatory T cells expressed the CD38 surface protein. They discovered that CD38 is expressed by iTfr cells but not by nTfr cells.
The team was also able to map out the specific position of iTfrs and nTfrs within the GCs along with showing their developmental path and capacity to support B cell function.
In March last year, a different CHOP-led study found that adding the proteasome inhibitor bortezomib to chemotherapy can considerably boost overall survival in children and young adults with newly diagnosed T-cell lymphoblastic lymphoma (T-LL).
