Upstream eventActivation/Proliferation, T-cells
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Covalent Protein binding leading to Skin Sensitisation||adjacent||High|
Life Stage Applicability
Key Event Relationship Description
After recognition of a non-self peptide (i.e. foreign) presented by dendritic cells, T-cells are activated and form memory T-cell, which proliferate. If reactivated upon hapten presentation by skin dendritic cells, these memory T-cells will induce allergic contact dermatitis).
This KER description is based only on the OECD document 2012 and needs updating.
Evidence Supporting this KER
It is well known, recognised and experimentally proved that skin sensitisation is a T-cell mediated immune response.
Using dinitrofluorobenzene and mice models, it was shown that cutaneous contact with reactive antigen induces KC/CXC chemokine ligand 1 production and neutrophil infiltration in an antigen, dose-dependent manner. The intensity of neutrophil infiltration into cutaneous antigen challenge sites, in turn, controls the number of antigen-primed T cells recruited into the site and the magnitude of immune response elicited.
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
- Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF. 2009. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64: 1699-1714.
- Engeman T, Gorbachev AV, Kish DD, Fairchild RL. 2004. The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites. J. Leukocyte Biol. 76:941-949.