T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases

• Published in: Nature (London) Vol. 427; no. 6970; pp. 154 - 159
• Main Authors: MEMPEL, Thorsten R, HENRICKSON, Sarah E, VON ANDRLAN, Ulrich H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 08-01-2004; Nature Publishing Group
• Subjects: Amino Acid Sequence; Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Cell Division; Cell Movement; Cells, Cultured; Cytokines; Dendritic Cells - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interferon-gamma - metabolism; Interleukin-2 - metabolism; Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphatic system; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microscopy; Molecular Sequence Data; Organs and cells involved in the immune response; T cell receptors; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Dendritic cell; Cellular immunity; Immune response; Lymph node; T-Lymphocyte
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02238

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 vitro. 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-gamma. 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.