Tonsils, lymph nodes, and the spleen all contain spherical collections of cells called germinal centers (GCs), which control the interactions between T follicular helper (Tfh) cells and B cells. Local FOXP3+ T follicular regulatory (Tfr) cells control the activity in these GCs.
Few studies have evaluated the biologic roles of human Tfr cells, and none have addressed where they come from or how they develop within tissues, despite the likelihood that Tfr cells’ proper function is crucial to immunologic health and that their dysfunction may contribute to a number of disease states.
Using a combination of computational, in vitro, and in vivo methodologies, the researchers, led by Carole Le Coz, PhD, a former postdoctoral researcher in the Romberg Lab, described the origins, functions, and positions of Tfr cells within GCs. Since GCs are located in secondary lymphoid tissues like lymph nodes, spleens, and tonsils, the researchers analyzed tonsils that had been removed from healthy donor patients.
Using an interlocking suite of single cell technologies, the researchers were able to show that there is one subpopulation of Tfr cells that is induced by Tfh cells, which they called iTfrs, and another subpopulation that were “naturally” derived from Tregs, a subpopulation of T cells that are responsible for moderating the immune system, which they called nTfrs. In doing so, the demonstrated that there are two developmental trajectories: Treg-to-nTfr and Tfh-to-iTfr.
Once the researchers identified these two subpopulations of Tfr cells, they analyzed whether these two regulatory T cells express the surface protein CD38 differently. They found that iTfr cells express CD38, whereas nTfr cells do not. They were also able to catalogue the precise location of these different subpopulations within the GCs, in addition to demonstrating their developmental path and ability so support B cell function.
