Abstract
Primary T-cell responses in lymph nodes (LNs) require contact-dependent information exchange between T cells and dendritic cells (DCs). Because lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool is composed of non-synchronized cells with different dwell times that display heterogeneous behaviour in mouse LNs in vitro1,2,3. Here we employ two-photon microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell time in LNs was synchronized. During the first 8 h after entering from the blood, T cells underwent multiple short encounters with DCs, progressively decreased their motility, and upregulated activation markers. During the subsequent 12 h T cells formed long-lasting stable conjugates with DCs and began to secrete interleukin-2 and interferon-γ. On the second day, coinciding with the onset of proliferation, T cells resumed their rapid migration and short DC contacts. Thus, T-cell priming by DCs occurs in three successive stages: transient serial encounters during the first activation phase are followed by a second phase of stable contacts culminating in cytokine production, which makes a transition into a third phase of high motility and rapid proliferation.
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Acknowledgements
We thank T. Buschman for software programming, H. Leung and B. Reinhardt for technical assistance, and D. Mathis, J. Lieberman and H. Ploegh for critical reading of the manuscript. This work was supported by grants from the NIH and the Dana Foundation Immuno-Imaging Program.
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Supplementary information
41586_2004_BFnature02238_MOESM1_ESM.pdf
Supplementary Figure 1: DCs are concentrated in close vicinity to high endothelial venules early after entry into LNs. (PDF 125 kb)
41586_2004_BFnature02238_MOESM2_ESM.pdf
Supplementary Figure 2: Absolute (a) and cumulative (b) contact duration between DO11.10 TCR transgenic CD4+ T cells and peptide-loaded DCs in popliteal lymph nodes. (PDF 26 kb)
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Supplementary Figure 3: Absolute and cumulative contact duration between P14 TCR transgenic CD8+ T cells and peptide-loaded DCs in popliteal lymph nodes. (PDF 23 kb)
41586_2004_BFnature02238_MOESM4_ESM.mov
Supplementary Movie 1A: Inhomogeneous distribution of Ag-loaded DCs and T cells in LNs early after LN entry. (MOV 5392 kb)
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Supplementary Movie 2: Homogenous distribution of DCs and rapid T cell migration in LNs late after LN entry. (MOV 12220 kb)
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Supplementary Movie 8: DCs (red) can undergo stable and dynamic interactions with T cells (green) simultaneously. (MOV 1164 kb)
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Mempel, T., Henrickson, S. & von Andrian, U. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427, 154–159 (2004). https://doi.org/10.1038/nature02238
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DOI: https://doi.org/10.1038/nature02238
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