Distinctive localization of antigen-presenting cells in human lymph nodes

Angel, Catherine E.; Chen, Chun-Jen J.; Horlacher, O; Winkler, Sintia; John, Thomas; Browning, Judy; MacGregor, Duncan; Cebon, Jonathan; Dunbar, P. Rod

doi:10.1182/blood-2008-06-165266

Cited by 77 publications

(99 citation statements)

References 49 publications

(84 reference statements)

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“…Accordingly, stroke facilitated the crosstalk between the brain and the immune system, and Ags such as MBP, but not MAP2 or NR-2A, were correlated with the initial severity of stroke. The cells loaded with brain-derived Ags were rare near blood vessels, but were found in the proximity of T cells and in areas stained with fibronectin, suggesting that bulk flow might be involved in the presence of brain Ags at the lymph nodes (28). The similarities between the findings at the PT and the CLN also supported that both lymphoid tissues were part of the lymphatic drainage of the CNS.…”

Section: Discussionsupporting

confidence: 65%

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

Planas

Gómez-Choco

Urra

et al. 2012

The Journal of Immunology

146

134

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In experimental animals, the presence of brain-derived constituents in cervical lymph nodes has been associated with the activation of local lymphocytes poised to minimize the inflammatory response after acute brain injury. In this study, we assessed whether this immune crosstalk also existed in stroke patients. We studied the clinical course, neuroimaging, and immunoreactivity to neuronal derived Ags (microtubule-associated protein-2 and N-methyl d-aspartate receptor subunit NR-2A), and myelin-derived Ags (myelin basic protein and myelin oligodendrocyte glycoprotein) in palatine tonsils and cervical lymph nodes of 28 acute stroke patients and 17 individuals free of neurologic disease. Stroke patients showed greater immunoreactivity to all brain Ags assessed compared with controls, predominantly in T cell zones. Most brain immunoreactive cells were CD68+ macrophages expressing MHC class II receptors. Increased reactivity to neuronal-derived Ags was correlated with smaller infarctions and better long-term outcome, whereas greater reactivity to myelin basic protein was correlated with stroke severity on admission, larger infarctions, and worse outcome at follow-up. Patients also had more CD69+ T cells than controls, indicative of T cell activation. Overall, the study showed in patients with acute stroke the presence of myelin and neuronal Ags associated with lymph node macrophages located near activated T cells. Whether the outcome of acute stroke is influenced by Ag-specific activation of immune responses mediated by CD69 lymphocytes deserves further investigation.

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Section: Discussionsupporting

confidence: 65%

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

Planas

Gómez-Choco

Urra

et al. 2012

The Journal of Immunology

146

134

View full text Add to dashboard Cite

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“…FRCs bundle collagen fibers to form 10-20 μm conduits that are in close proximity to an extensive network of DCs that directly sample antigen carried by the lymph for presentation to naïve T cells [60]. These conduits direct antigen and APCs towards high endothelial venules, a specialized vasculature that promotes the delivery of naïve T cells into the LN.…”

Section: Secondary Lymphoid Organsmentioning

confidence: 99%

“…Upon reaching the LN, T Reg cells preferentially migrate to the paracortex where they interact with CD8α + DCs and tissue derived CD11b − CD8α − DCs [82]. CD8α + DCs, which are critical for peripheral cross-tolerance to soluble antigen, cluster with T Reg cells in the paracortical area of the LN [60,82]. The role of CCR7 in coordinating these interactions is again highlighted by studies in CCR7 −/− mice, which exhibit impaired T Reg cell positioning and loss of their ability to promote tolerance and prevent autoimmune pathologies [83,84].…”

Section: Lymphoid Organs In Peripheral Tolerancementioning

confidence: 99%

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Lund

Swartz

2010

J Mammary Gland Biol Neoplasia

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Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

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“…12 In mice, extensive DC-subset analyses have been performed through the use of transgenic models, the ability to track and monitor cells in vivo, and the ability to remove specific organs, whereas in humans, especially for DC subsets present at low frequencies in lymphoid tissues such as lymph nodes (LNs; 0.1%-2%), this is more complicated. [13][14][15] Because skin is generally regarded an attractive site for the delivery of vaccines, identification and characterization of DC subsets in skin-draining LN are particularly relevant. Although the authors of previous immunohistochemical studies have indicated the presence of both Langerhans cells (LCs) and dermal DCs (DDCs) in steady-state skin-draining LNs, 14,15 until now it has proven technically unfeasible to perform more extensive flow cytometry-based phenotypic and functional cDC subset analyses.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Because skin is generally regarded an attractive site for the delivery of vaccines, identification and characterization of DC subsets in skin-draining LN are particularly relevant. Although the authors of previous immunohistochemical studies have indicated the presence of both Langerhans cells (LCs) and dermal DCs (DDCs) in steady-state skin-draining LNs, 14,15 until now it has proven technically unfeasible to perform more extensive flow cytometry-based phenotypic and functional cDC subset analyses.…”

Section: Introductionmentioning

confidence: 99%

Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation

Ven¹,

Hout²,

Lindenberg³

et al. 2011

Blood

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To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a ؉ subsets were identified as most likely skin-derived CD11c int Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11c hi dermal DCs with variable expression of langerin. Two other CD1a ؊ LNresiding cDC subsets were characterized as CD14 ؊ BDCA3 hi CD103 ؊ and CD14 ؉ BDCA3 lo CD103 ؉ , respectively. Whereas the CD1a ؉ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFN␥ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a ؊ cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies. (Blood. 2011;118(9):2502-2510) IntroductionDendritic cells (DCs) are the most powerful APCs and play critical roles in keeping the balance between immune tolerance and activation. DCs are therefore also important for starting an efficient antitumor immune response and are seen as promising targeting candidates for tumor immunotherapy strategies. 1,2 Current DCbased immunotherapies generally use ex vivo-generated autologous monocyte-derived or CD34 ϩ hematopoietic precursorderived DCs. 2,3 Despite occasionally observed clinical benefits from DC-based vaccination, there is a large gap between the actual and expected efficacy of such trials on the basis of in vivo animal experiments. 4 Many questions remain as to which DC type to use, how to stimulate them, or where best to administer the DCs to achieve vaccination with mature, migratory, and Th1-inducing DCs that provoke an efficient antitumor immune response. [5][6][7] An ever-increasing insight in specialized functions of murine DC subsets is sadly mirrored by a lack of knowledge on how human DCs relate to mouse DCs and whether subsets that have been identified in mice have a (phenotypically different, but functionally equivalent) counterpart in humans. 4,[8][9][10][11] In particular the interrelationship between nonplasmacytoid, conventional DC (cDC) subsets has been obscure, in large part because of their plasticity and dynamic changes in their differentiation and maturation state, which is accompanied by shifts in associated phenotypic markers. 12 In mice, extensive DC-subset analyses have been performed through the use of transgenic models, the ability ...

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Distinctive localization of antigen-presenting cells in human lymph nodes

Cited by 77 publications

References 49 publications

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation

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