T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases (original) (raw)
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Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity
Nature Immunology, 2004
Induction of immunity and peripheral tolerance requires contacts between antigen-bearing dendritic cells (DCs) and cognate T cells. Using real-time two-photon microscopy, we have analyzed the dynamics of CD8 + T cells in lymph nodes during the induction of antigen-specific immunity or tolerance. At 15-20 h after the induction of immunity, T cells stopped moving and established prolonged interactions with DCs. In tolerogenic conditions, despite effective initial T cell activation and proliferation, naive T cells remained motile and established serial brief contacts with multiple DCs. Thus, stable DC-T cell interactions occur during the induction of priming, whereas brief contacts may contribute to the induction of T cell tolerance.
Nature Immunology, 2005
The maturation status of dendritic cells (DCs) determines whether they prime or tolerize T cells. We targeted ovalbumin peptide exclusively to DCs in situ using an antibody to DEC-205 and studied the interaction of DCs with naive CD4 + T cells in tolerizing or priming conditions. We used two-photon microscopy to simultaneously track antigen-specific OT-II T cells, nonspecific T cells and DCs in lymph nodes of living mice. In both tolerance and immunity, OT-II cells arrested on DCs near high endothelial venules beginning shortly after extravasation and regained their baseline speed by 18 h. Thus, early antigen-dependent T cell arrest on DCs is a shared feature of tolerance and priming associated with activation and proliferation.
Active dissemination of cellular antigens by DCs facilitates CD8(+) T-cell priming in lymph nodes
European journal of immunology, 2017
Antigen (Ag)-specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their co-localization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8(+) T cell-DC interactions to study the sites, routes and cells mediating Ag transfer in mice. In vitro, Ag transfer from isolated ovalbumin (OVA)(+) bone marrow (BM)-DCs triggered widespread arrest, Ca(2+) flux and CD69 upregulation in OT-I T cells contacting recipient DCs. Intravital two-photon imaging revealed that survival of Ag-donor DCs in LNs was required for Ag dissemination among resident CD11c(+) DCs. Upon interaction with recipient DCs, CD8(+) T cells clustered, upregulated CD69, proliferated and differentiated into effectors. Few DCs sufficed for activation, and for efficient Ag dissemination LFA-...
Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes
Nature immunology, 2003
The cellular dynamics underlying activation of CD8 + T cells by dendritic cells (DCs) in the lymph node are not known. Here we have tracked the behavior of T cells and DCs by subjecting intact lymph nodes to real-time two-photon microscopy. We show that DCs scan at least 500 ...
Characterizing the Dynamics of CD4+ T Cell Priming within a Lymph Node
Generating adaptive immunity postinfection or immunization requires physical interaction within a lymph node T zone between Ag-bearing dendritic cells (DCs) and rare cognate T cells. Many fundamental questions remain regarding the dynamics of DC-CD4+ T cell interactions leading to priming. For example, it is not known how the production of primed CD4+ T cells relates to the numbers of cognate T cells, Ag-bearing DCs, or peptide-MHCII level on the DC. To address these questions, we developed an agent-based model of a lymph node to examine the relationships among cognate T cell frequency, DC density, parameters characterizing DC-T cell interactions, and the output of primed T cells. We found that the output of primed CD4+ T cells is linearly related to cognate frequency, but nonlinearly related to the number of Ag-bearing DCs present during infection. This addresses the applicability of two photon microscopy studies to understanding actual infection dynamics, because these types of experiments increase the cognate frequency by orders of magnitude compared with physiologic levels. We found a trade-off between the quantity of peptidemajor histocompatibility class II on the surface of individual DCs and number of Ag-bearing DCs present in the lymph node in contributing to the production of primed CD4+ T cells. Interestingly, peptide-major histocompatibility class II t 1/2 plays a minor, although still significant, role in determining CD4+ T cell priming, unlike the primary role that has been suggested for CD8+ T cell priming. Finally, we identify several pathogen-targeted mechanisms that, if altered in their efficiency, can significantly effect the generation of primed CD4+ T cells.
Journal of Experimental Medicine, 2003
Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7−/− DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor n...
Immunity, 2000
the minimum contact time between TCR and surfacebound cognate peptide-MHC complexes was established in the range of 20 hr (Iezzi et al., 1998). The minimum duration of TCR signaling required by naive T cells is lowered to 6 hr in the presence of mature DC (Lanzarzburg vecchia et al., 1999) or to 2 hr for preactivated T hybridoma cells in the presence of macrophages (Underhill et Josef-Schneider Str. 2 al., 1999). It has also been shown that interaction of the TCR with plate-bound cognate MHC molecules induces 97080 Wü rzburg Germany migratory arrest in T lymphocytes provided by LFA-1/ ICAM-1-mediated adhesion (Dustin et al., 1997). The † Institute of Immunology University of Witten/Herdecke transition from a migratory to a sessile state is a prerequisite for the formation of a tight and highly organized ‡ Department of Dermatology University of Mü nster interaction and signaling zone between T cell and APC, termed supramolecular activation cluster (SMAC) (Monks Germany et al., 1998) or "immunological synapse" (Grakoui et al., 1999). A central portion of the interaction plane contains TCR, CD3, CD4 or CD8, CD2, and CD28, as well as signal-Summary ing molecules (e.g., Lck, Fyn, Zap70, PKC, MEKK2), whereas an outer ring-like zone is enriched for adhesion Cognate interactions of naive T cells with antigenpresenting dendritic cells require physical cell-cell molecules LFA-1 and ICAM-1 (Monks et al., 1997, 1998; Shaw and Dustin, 1997; Dustin and Shaw, 1999; Pen-contacts leading to signal induction and T cell activation. Using a three-dimensional collagen matrix video-ninger and Crabtree, 1999; Schaefer et al., 1999).
Active dissemination of cellular antigens by DCs facilitates CD8 + T‐cell priming in lymph nodes
European Journal of Immunology, 2017
Antigen (Ag) specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their colocalization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8 + T cell-DC interactions to study the sites, routes, and cells mediating Ag transfer in mice. In vitro, Ag transfer from isolated ovalbumin (OVA) + bone marrow (BM) DCs triggered widespread arrest, Ca 2+ flux, and CD69 upregulation in OT-I T cells contacting recipient DCs. Intravital two-photon imaging revealed that survival of Ag-donor DCs in LNs was required for Ag dissemination among resident CD11c + DCs. Upon interaction with recipient DCs, CD8 + T cells clustered, upregulated CD69, proliferated and differentiated into effectors. Few DCs sufficed for activation, and for efficient Ag dissemination lymphocyte function associated antigen 1 (LFA-1) expression on recipient DCs was essential. Similar findings characterized DCs infected with a replication-deficient OVA-expressing Vaccinia virus known to downregulate MHC-I. Overall, active Ag dissemination from live incoming DCs helped activate CD8 + T cells by increasing the number of effective presenting cells and salvaged T-cell priming when Ag-donor DCs could not present Ag.