Table 3.

Conclusions from intravital imaging studies of lymphocytes in mouse lymph nodes

Number	Conclusion
1	Lymph nodes are major sites of antigen capture, detection and adaptive immune responses. T cells recruited to lymph nodes can spend a few hours to 1 day sampling APCs for antigen, but they frequently leave the nodes without finding antigen
2	While encounters between T cells and their specific antigens occur randomly, the frequency of such encounters is enhanced by the expression of antigen-specific TCRs on T cells and the ability of most T cells to recirculate through lymph nodes at least once per day. This recirculation permits populations of both naive T cells and memory T cells to scan lymph nodes (and other lymphoid tissues) on a daily basis for the presence of pathogens and eliminate them if necessary
3	Prolonged T-cell–DC contacts arise when several T cells congregate around individual DCs. After 16–24 hr in a lymph node, activated CD4+ T cells resume their motility, pursue several rounds of proliferation, and then interact with cognate B cells located proximal to a follicle
4	The strategic use of photoactivatable probes, which can tag cells present in one location and image them while enroute to another site, have shown that the extent of T-cell–DC interactions in a given zone of a lymph node influences the migration of T cells to another zone(s)
5	Upon migration in a lymph node, B cells may adhere to T cells and drag the T cells behind them. T-cell–B-cell contacts of sufficient time and strength are required to stimulate T-cell signals (e.g. CD40 ligand, cytokines). During recognition of these signals by antigen-activated B cells, T cells depolarize and then adhere to and follow the B cells
6	In response to increased expression of adhesion molecules, chemokines and chemokine receptors in T-cell zones of lymph nodes, naive CD4+ T cells migrate more rapidly than other cell types through high endothelial venules into regions where antigens are displayed by DCs. T cells may spend between a few hours to a day in these regions, and their entry and exit from a lymph node is mediated by the chemokine receptor CCR7 and sphingosine-1-phosphate receptor 1, respectively
7	Local T-cell motility in a lymph node can transform into long-range migrations by T cells that leave this tissue and migrate in blood or lymph to distant sites
8	The duration of contact between T cells with DCs or B cells in a lymph node determines the extent of immune responsiveness. The capacity of regulatory T cells to down-regulate CD4+ T-cell priming and ability of inhibitory receptors on T cells to block CD8+ effector T-cell activity is mediated by the increased surface expression of CTLA-4 and PD-1. By reducing the time of effective cell–cell contact between T cells and antigen-bearing DCs or B cells and the time that cellular receptors remain engaged, the inhibitory effects of CTLA-4 and PD-1 are amplified upon signalling through the TCR or costimulatory molecules

APCs, antigen-presenting cells; CTLA-4, cytotoxic T-lymphocyte antigen 4; DCs, dendritic cells, PD-1, programmed death 1; TCR, T-cell receptor.