IL-2 producing T Follicular Helper cells self restricts entry of T follicular helper cells in the germinal centers

Abstract Upon infection or immunization, dendritic cells (DCs) present antigens (Ags) to naïve CD4 +T cells. As a result, fraction of the responding upregulate Bcl6 and differentiate into T follicular helper (Tfh) cells, which migrate B cell follicles. Once in follicles, Tfh help promote development maintenance germinal centers (GC). Importantly, limiting number is critical for maintaining selective pressure GC, thereby allowing Darwinian selection that leads affinity maturation. However, mechanisms regulate numbers prevent excessive remains unknown. Using an influenza virus model, we show here differentiation limited first 72h infection. After this time, whereas DCs continue viral efficiently prime fail preferentially effector Th1 Mechanistically, demonstrate lack after day three was due presence early-primed Our results indicate produce large amounts IL-2 proximity new three. Collectively, our data act as self-regulating factor shields follicles early infection, preventing continuous regardless antigens. These self-competitive mechanism critically contributes expansion This work supported by The University Alabama at Birmingham (UAB) National Institutes Health grant 1R01AI162698-01A1 A.B.-T