Cargando…

Thromboxane A2 acts as tonic immunoregulator by preferential disruption of low-avidity CD4(+) T cell–dendritic cell interactions

Interactions 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 ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Moalli, Federica, Cupovic, Jovana, Thelen, Flavian, Halbherr, Pascal, Fukui, Yoshinori, Narumiya, Shuh, Ludewig, Burkhard, Stein, Jens V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267235/
https://www.ncbi.nlm.nih.gov/pubmed/25488981
http://dx.doi.org/10.1084/jem.20140137
Descripción
Sumario:Interactions 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 (T(FH)), 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.