Journal
FRONTIERS IN IMMUNOLOGY
Volume 6, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2015.00559
Keywords
T cell motility; intravital imaging; thromboxane A2; T cell-DC interactions; Myo1g
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Funding
- Swiss National Foundation grants [31003A_135649, CR23I3_156234, CRSII3_141918]
- FP7 Marie Curie RG grant [276702]
- Swiss Cancer League grant [KFS-3524-08-2014]
- Swiss National Science Foundation (SNF) [CR23I3_156234, CRSII3_141918] Funding Source: Swiss National Science Foundation (SNF)
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It is well established that the balance of costimulatory and inhibitory signals during interactions with dendritic cells (DCs) determines T cell transition from a naive to an activated or tolerant/anergic status. Although many of these molecular interactions are well reproduced in reductionist in vitro assays, the highly dynamic motility of naive T cells in lymphoid tissue acts as an additional lever to fine-tune their activation threshold. T cell detachment from DCs providing suboptimal stimulation allows them to search for DCs with higher levels of stimulatory signals, while storing a transient memory of short encounters. In turn, adhesion of weakly reactive T cells to DCs presenting peptides presented on major histocompatibility complex with low affinity is prevented by lipid mediators. Finally, controlled recruitment of CD8(+) T cells to cognate DC-CD4(+) T cell clusters shapes memory T cell formation and the quality of the immune response. Dynamic physiological lymphocyte motility therefore constitutes a mechanism to mitigate low avidity T cell activation and to improve the search for optimal DCs, while contributing to peripheral tolerance induction in the absence of inflammation.
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