Dynamic Imaging of T Cell-Dendritic Cell Interactions in Lymph Nodes

Stoll, Sabine; Delon, Jérôme; Brotz, Tilmann M.; Germain, Ronald N.

doi:10.1126/science.1071065

Cited by 656 publications

(564 citation statements)

References 28 publications

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“…The absence of this specialized matrix in the iris stroma likely contributes to the slower speed that we observed for T cells migrating in the iris. Estimates of the average lateral speed of T cells in lymph node vary from 4 µm/min during an activation phase to about 11 µm/min in the absence of an antigenic challenge [4,6,33]. These are considerably faster than the 1-2 µm/min lateral speed reported here and likely reflect tissue-specific differences in the nature of chemotactic signals and/or the extracellular matrix along which the cells must navigate.…”

Section: Discussionmentioning

confidence: 52%

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T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Rosenbaum

Ronick

Song

et al. 2008

Clinical Immunology

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Videomicroscopy is being used increasingly to characterize the interaction of T cells and antigenpresenting cells (APCs) within lymphatic tissues but has not been reported, to our knowledge, at sites of inflammation. We employed intravital videomicroscopy to study an anterior uveitis model using DO11.10 T cells and ovalbumin (OVA). T cell movement in iris was consistent with a random walk independent of the presence of recognized antigen and had a lateral speed slower than T cells in lymph node. Lingering of T cells adjacent to APCs suggested that they were physically interacting. This apparent contact demonstrated antigen specificity when comparing results from DO11.10 cells with OVA versus bovine serum albumin (BSA) loaded APCs but not when comparing results from OVA-loaded APCs with DO11.10 versus HA clonotype 6.5 T cells. Further studies with this model system should clarify the contribution of T cell-APC communication at a site of inflammation, infection, or immunization.

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Section: Discussionmentioning

confidence: 52%

“…More recently in vivo documentation of T cell and APC trafficking and interactions have been documented, especially through the use of two photon confocal microscopy [4,5,6,7,8,9]. The majority of these studies involve the lymph node or other lymphoid organ such as the bone marrow or thymus [10,11].…”

Section: Introductionmentioning

confidence: 99%

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Rosenbaum

Ronick

Song

et al. 2008

Clinical Immunology

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“…LPS, bacterial CpG DNA and double-stranded viral DNA) and large amounts of antigen. As a consequence, maturing DC rapidly up-regulate chemokine receptors, which favor their migration to the draining lymph nodes at a time at which IL-12 is maximally produced [56]. Here, early activated DC should rapidly induce CD4 + T cell activation [57], possibly Th1 polarization [46], and even faster priming of potent CTL [58,59] with Tc1 phenotype [29].…”

Section: Discussionmentioning

confidence: 99%

Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

Boni¹,

Iezzi

Degl’Innocenti³

et al. 2006

Eur J Immunol

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Dendritic cell (DC) maturation influences the priming and polarization of T lymphocytes. We recently found that early activated DC (i.e. DC exposed to promaturation stimuli for 8 h) were more prone to prime in vivo a type-1 cytotoxic T cell (Tc1) response than DC exposed to pro-maturation stimuli for 48 h (48h-DC). We investigated whether 48h-DC, conversely, allowed the induction of Tc2 cells. Antigenpulsed mouse bone-marrow-derived DC at any maturation stage, in the presence of exogenous IL-12, skewed in vitro naive CD8 + T cells towards Tc1 cells, but 48h-DC most potently, in the presence of exogenous IL-4, favored the induction of Tc2 cells. In vivo, full maturation of DC promoted expansion of Tc2 and fall of Tc1 cells. Tc2 cells maintained a high cytolytic activity and produced significant amounts of IL-4, IL-5, IL-10 and TGF-b. Our results indicate that polarization of naive CD8 + T cells to Tc2 cells is dependent on the amount of time DC have been exposed to maturation stimuli, and might be favored in late and/or chronic phases of an immune response.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35597_s.pdf IntroductionUpon antigenic stimulation, T lymphocytes proliferate and acquire a variety of effector functions. Indeed, activation of naive CD4 + T cells in the presence of IL-12 results in the development of Th1 cells, which mainly secrete interferon (IFN)-c, interleukin (IL)-2, tumor necrosis factor (TNF)-a and lymphotoxin, and are commonly associated with a cell-mediated immune response. Conversely, the presence of IL-4 skews the Th response towards Th2 cells producing IL-4, IL-10 and IL-13, relevant cytokines against helminthiasis and allergic diseases [1]. More recently, a third subset of CD4 + T cells has been identified, which express CD25, produce IL-10 and TGF-b, and display regulatory functions [2].The polarization of CD8 + CTL has been less characterized [3]. IL-12 also appears to be critical for the generation of Tc1 cells, characterized by a high production level of IFN-c and cytolytic activity, CC chemokine receptor (CCR)5 expression and the ability to migrate to the inflamed tissues where they are [16], and in many cases their presence was associated with disease severity and progression [13][14][15][16]. In mouse tumor models, IL-4-transduced tumor cells elicited potent antitumor activities [17] and induced Tc2 cells able to cure lung metastases [5,17]. IL-4 produced by CTL was required for the generation of protective tumor-associated CD8 + T cells [5,18]. In other models, Tc2 cells were far less effective in curing subcutaneous tumors [19,20] and lung metastases [21]. Finally, CD8 + T cell subpopulations exhibiting regulatory function have also been described [14,22].Dendritic cells (DC), professional antigen presenting cells (APC) with a unique ability in priming T cell responses [23], play a key role in T cell polarization. In particular, it has been reported that subsets of DC, derived from distinct precursors, induce differenti...

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“…And he suggested that the random movement has a purpose, by helping a T cell range across a broad territory and find the 'antigen-presenting cell' carrying the precise antigen it recognizes. In 2002, the work was published in Science 2 as part of a trio of advanced microscopy papers exploring the dynamics of T cells 3,4 .…”

Section: Special Effectsmentioning

confidence: 99%

Immunology: Lights, camera, infection

Erdmann¹

2009

Nature

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Behind the heavy black curtains of his microscopy room, Mark Miller is shooting an action movie. He gives the settings on the multiphoton microscope a onceover while his senior scientist Vjollca Konjufca checks the sedated mouse on the warmed stage. Then Miller flicks a switch on the scanner and red, blue and green images flicker on the computer monitor. He points to what he's looking for. "Right there, " he says. Blue-labelled Salmonella bacteria gather near the top of a red villus, a finger-like projection from the wall of the mouse's small intestine. The bacteria look like helicopters buzzing around a mountain. It's early afternoon, and we are settling in to watch these bacteria for the next hour.Miller's experiments, and others like it, are not just gripping the audience behind the curtain -they are gripping a much broader audience of immunologists. Miller, at Washington University School of Medicine in St Louis, Missouri, runs one of the leading labs using multiphoton microscopy to watch infections in living animals in real time.Less than a decade ago, Miller and other immunologists mostly studied the process of infection in vitro, mixing pathogens and the cells they interact with in a culture dish. These simulations had their limits because the cells, much like animals in a zoo, were removed from the environment that influences their behaviour. The advent of multiphoton microscopy allowed researchers to view deep inside living tissues and watch cell biology live and 'in the wild' . This is particularly valuable for the

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Dynamic Imaging of T Cell-Dendritic Cell Interactions in Lymph Nodes

Cited by 656 publications

References 28 publications

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type‐2 cytotoxic T lymphocytes

Immunology: Lights, camera, infection

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