Naive T cells must interact with dendritic cells (DCs) — the professional antigen-presenting cells of the immune system — to become activated. The dynamics of T-cell–DC interactions have been examined in several studies using excised lymph nodes, in which lymph and blood flow were not maintained, and the results have been variable. In a new study published in Nature, Ulrich von Andrian's group used two-photon microscopy to study T-cell-DC interactions in vivo in the intact popliteal lymph nodes (PLNs) of anaesthetized mice, in which blood and lymph flow were maintained, and show that T-cell migration occurs in three distinct phases.

Mice were injected with fluorescence-labelled DCs into the footpad, and by the following day, DCs had accumulated in the PLNs. Lipopolysaccharide was co-administered with DCs to induce the expression of CC-chemokine receptor 7 (CCR7) by the DCs, which allows them to home to lymph nodes. Eighteen hours after DC injection, T-cell-receptor-transgenic CD8+ T cells were injected intravenously. Two hours after injection, the transgenic T cells had migrated to the PLNs and constituted 1–2% of T cells.

Where do the injected DCs localize in the PLNs? The authors found that many of the DCs localized around high endothelial venules (HEVs) — a site that allows the DCs to interact with T cells as they enter the node.

Analysis of T-cell dynamics revealed that T cells interact with DCs in three distinct phases. In phase one, covering the first eight hours after T-cell entry to the PLNs, T cells formed brief contacts with DCs that lasted for less than 30 minutes. These interactions resulted in increased expression of early activation markers by the T cells. Phase two covered the 8–24-hour period after T-cell transfer. In this phase, T cells formed stable contacts with DCs that lasted for more than an hour. The T cells expressed activation markers and secreted interleukin-2 and interferon-γ. In phase three, which started after 24 hours, the T cells dissociated from DCs, and underwent rapid migration and proliferation. When transgenic CD4+ T cells were used, a similar three-phase pattern of interactions was observed.

It remains to be determined what mechanisms control the phase-to-phase transition and how the length of the interactions is controlled.