Moalli, FedericaFedericaMoalliCupovic, JovanaJovanaCupovicThelen, FlavianFlavianThelenHalbherr, PascalPascalHalbherrFukui, YoshinoriYoshinoriFukuiNarumiya, ShuhShuhNarumiyaLudewig, BurkhardBurkhardLudewigStein, Jens VolkerJens VolkerStein2024-10-232024-10-232014-12-15https://boris-portal.unibe.ch/handle/20.500.12422/131645Interactions between dendritic cells (DCs) and T cells control the decision between activation and tolerance induction. Thromboxane A2 (TXA2) and its receptor TP have been suggested to regulate adaptive immune responses through control of T cell-DC interactions. Here, we show that this control is achieved by selectively reducing expansion of low-avidity CD4(+) T cells. During inflammation, weak tetramer-binding TP-deficient CD4(+) T cells were preferentially expanded compared with TP-proficient CD4(+) T cells. Using intravital imaging of cellular interactions in reactive peripheral lymph nodes (PLNs), we found that TXA2 led to disruption of low- but not high-avidity interactions between DCs and CD4(+) T cells. Lack of TP correlated with higher expression of activation markers on stimulated CD4(+) T cells and with augmented accumulation of follicular helper T cells (TFH), which correlated with increased low-avidity IgG responses. In sum, our data suggest that tonic suppression of weak CD4(+) T cell-DC interactions by TXA2-TP signaling improves the overall quality of adaptive immune responses.en600 - Technology::610 - Medicine & health500 - Science::570 - Life sciences; biologyarticle10.7892/boris.663632548898110.1084/jem.20140137