Two Distinct T Cell Lineages Identified

Children’s Hospital of Philadelphia (CHOP) published a new study in Science Immunology shedding light on the origins of two different T cell lineages, one related to autoimmunity and the other to protective immunity. These findings could pave the way for new therapies for diseases targeting the immune system.

The prevailing wisdom has been that suppressing the immune system broadly is the only way to stop inflammation, making patients more susceptible to infection. However, this study shows that T cells come from two different places, allowing the suppression of inflammation due to autoimmunity while allowing T cells that fight infection to thrive.

The researchers used a combination of computational, in vitro, and in vivo techniques to describe the origins, functions, and positions of T follicular regulatory (Tfr) cells within germinal centers (GCs) located in tonsils, lymph nodes, and spleens. Using an interlocking suite of single-cell technologies, they identified two subpopulations of Tfr cells: one induced by Tfh cells, called iTfrs, and the other derived from Tregs, called nTfrs. They also found that iTfr cells express CD38, whereas nTfr cells do not.

The study raises the question of whether we could selectively deplete iTfr cells through anti-CD38 treatments while leaving nTfrs intact to target specific T cells with a “silver bullet” rather than a “bomb.” The researchers also suggest that a similar approach could potentially be used in a therapeutic context to boost immunity in patients with weakened immune systems.

These findings have implications for developing targeted therapies for autoimmune diseases. Suppressing inflammation without making patients more susceptible to infection opens another avenue of research worth pursuing.