Abstract
SummaryThe interaction of T cells with dendritic cells (DCs) determines whether an immune response is launched or not. Recognition of antigen leads to formation of immunological synapses at the interface between the cells. The length of interaction is likely to determine the functional outcome, because it limits the number of MHC class II-peptide complexes that can be recruited into the synapse. Here, we show that regulatory T (Treg) cells and naive helper T (Th) cells interact differently with DCs in the absence of proinflammatory stimuli. Although differences in T cell receptor repertoire might contribute, Foxp3-induced phenotypic differences play a major role. We found that Neuropilin-1 (Nrp-1), which is expressed by most Treg cells but not naive Th cells, promoted prolonged interactions with immature DCs (iDCs), resulting in higher sensitivity to limiting amounts of antigen. This is likely to give Treg cells an advantage over naive Th cells, with the same specificity leading to a “default” suppression of immune responses in the absence of “danger signals.”
Highlights
The interaction between helper T (Th) cells and dendritic cells (DCs) has been studied extensively
T cell receptor (TCR) molecules are recruited to the central area of the synapse into central supramolecular activation clusters, whereas several adhesion molecules accumulate in the peripheral area of the synapse (Monks et al, 1998)
Foxp3 modulates a multitude of genes (Hill et al, 2007), and we demonstrated that one of them, Neuropilin-1 (Nrp-1), which is expressed by Treg cells but not naive Th cells (Bruder et al, 2004), played a key role in promoting long interactions between Treg cells and immature DCs (iDCs)
Summary
The interaction between helper T (Th) cells and dendritic cells (DCs) has been studied extensively. The contact zone between DCs and T cells is often referred to as immunological synapse (Friedl et al, 2005). The molecular interactions within these synapses are dynamic, revealing different patterns of interactions between surface molecules depending on the presence or absence of antigen, the activation status of T cells and DCs, and the temporal stage of the immune response (Friedl et al, 2005). T cell receptor (TCR) molecules are recruited to the central area of the synapse into central supramolecular activation clusters (cSMACs), whereas several adhesion molecules accumulate in the peripheral area of the synapse (pSMAC) (Monks et al, 1998). TCR molecules initially form microclusters, which converge to form the cSMAC (Krummel et al, 2000). It has been proposed that TCR microclusters, which continuously form in the periphery, initiate and sustain signaling, whereas their movement to the cSMAC is associated with
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
