Correlation between Lymphocyte Proliferative Responses and Dendritic Cell Migration in Regional Lymph Nodes following Skin Painting with Contact-Sensitizing Agents

An optimized non-invasive imaging modality capable of tracking and quantifying in vivo DC migration in patients would provide clinicians with valuable information regarding therapeutic DC-based vaccine outcomes. Superparamagnetic iron oxide (SPIO) nanoparticles were used to label bone marrow-derived DC. In vivo DC migration was tracked and quantified non-invasively using cellular magnetic resonance imaging (MRI) in a mouse model. Labelling DC with SPIO reflects the kinetics of DC migration in vivo but appears to reduce overall DC migration, in part due to nanoparticle size. Magnetic separation of SPIO-labelled (SPIO(+)) DC from unlabelled (SPIO(-)) DC prior to injection improves SPIO(+) DC migration to the lymph node. Corresponding MR image data better correlate with the presence of DC in vivo; an improved immunological response is also seen. Cellular MRI is a viable, non-invasive imaging tool that can routinely track DC migration in vivo. Consideration should be given to optimizing MRI contrast agent-labelling of clinical-grade DC in order to accurately correlate DC fate to immunological outcomes in patients.

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“…8). This data supports the idea that more DC migration generates a greater functional T cell response in vivo 36.…”

Section: Resultssupporting

confidence: 87%

Labelling dendritic cells with SPIO has implications for their subsequent in vivo migration as assessed with cellular MRI

Chickera¹,

Snir²,

Willert³

et al. 2011

Contrast Media & Molecular

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“…Increases in the cellularity of lymph nodes draining sites of virus infection have been attributed to both recruitment of CD8 + cytotoxic lymphocyte precursors and bystander proliferation (Blacklaws et al, 1995;Hamilton-Easton and Eichelberger, 1995;Tripp et al, 1995). Kimber et al (1990) described a correlation between the primary T cell proliferative response and the accumulation of migratory DC within the local lymph node draining the site of application of the contact sensitizers FITC and Rhodamin B. The increased total lymph node cell numbers we observed after infection with live virus may well be due to the increased numbers of antigen-bearing DC arriving in the node and stimulating primary virus-speci®c T lymphocyte proliferation.…”

Section: Discussionmentioning

confidence: 68%

Langerhans Cells Migrate to Local Lymph Nodes Following Cutaneous Infection with an Arbovirus

Johnston

Halliday

King

2000

Journal of Investigative Dermatology

195

148

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Whereas there has been recent interest in interactions between dendritic cells and pathogenic viruses, the role of dendritic cells in the initiation of protective immunity to such organisms has not been elucidated. The aim of this study was to examine whether a resident dendritic cell population in the skin, Langerhans cells, respond to cutaneous viral infections which are effectively cleared by the immune system. We therefore characterized the ability of Langerhans cells to migrate to local draining lymph nodes following infection with the arthropod-borne viruses, West Nile virus or Semliki Forest virus. The data show that major histocompatibility complex class II+/NLDC145+/E-cadherin+ Langerhans cell numbers are increased in the draining lymph nodes of infected mice and this increase is accompanied by a concomitant decrease in the Langerhans cell density in the epidermis. Langerhans cell migration is associated with an accumulation of leukocytes in the lymph node, which is one of the earliest events in the initiation of an immune response. Both the migratory response and the draining lymph node leukocyte accumulation were abrogated if ultraviolet-inactivated instead of live viruses were used, suggesting the activation and subsequent migration of Langerhans cells requires a live, replicating antigen. Our findings are likely to have wider implications for the development of epidermally delivered vaccines and suggest that mobilization of dendritic cells may be involved in the development of immune responses to arthropod-borne viruses.

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“…A decrease of epidermal LC numbers is also found after application of non‐anoic acid (13). In mice, LC migration is required for the induction of and directly related to the amount of cell proliferation in the local lymph node assay (43). Local LN cell proliferation is induced by irritating concentration of non‐sensitizers, such as SDS (44,45) and non‐anoic acid (46).…”

Section: Discussionmentioning

confidence: 99%

Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration

Jacobs

Lehé

Hasegawa

et al. 2006

Experimental Dermatology

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Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.

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Correlation between Lymphocyte Proliferative Responses and Dendritic Cell Migration in Regional Lymph Nodes following Skin Painting with Contact-Sensitizing Agents

Cited by 37 publications

References 18 publications

Labelling dendritic cells with SPIO has implications for their subsequent in vivo migration as assessed with cellular MRI

Labelling dendritic cells with SPIO has implications for their subsequent in vivo migration as assessed with cellular MRI

Langerhans Cells Migrate to Local Lymph Nodes Following Cutaneous Infection with an Arbovirus

Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration

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