Delayed-Type Hypersensitivity Model

Delayed-type hypersensitivity (DTH) reactions, also known as type IV hypersensitivity reactions, are mediated by soluble or cell-associated antigens primarily involving CD4+ or CD8+ T cell activation. These reactions are characterized by the release of mediators from activated T cells. The T cells then activate local endothelial cells and recruit macrophages, which results in local inflammation and swelling. There are three major categories of DTH reactions, classified by delivery of the antigen: injected into the skin, absorbed into the skin or absorbed through the gut. We have validated study models to enable the testing of compounds targeting DTH in the skin resulting from either injection or absorption of the antigen:

  • DTH induced by intraperitoneal injection of keyhole limpet hemocyanin (KLH) (standard strain and humanized mouse)
  • DTH induced by topical application of oxazolone
KLH-induced DTH Model

On Day 1, mice are immunized by an intraperitoneal injection with a KLH/CFA/IFA emulsion. On Day 7 (0h), following baseline ear thickness measurements, mice are challenged with KLH by injecting into the ear. Ear swelling is then measured on Day 8 (24h), Day 9 (48h) and Day 10 (72h).

Oxazolone DTH Model

On Day 1, animals get three topical applications of oxazolone on the abdominal skin. On Day 5, topical application of oxazolone is done on the ear. Ear swelling is then measured on Day 6 (24h), Day 7 (48h) and Day 8 (72h).

Optional endpoints for DTH models:

  • PK/PD blood collections
  • Cytokine/chemokine analysis
  • Clinical chemistry
  • Histopathological evaluation
  • Immunohistochemistry
  • Flow cytometry in lymph nodes or spleen
  • Use of ‘humanized mice’ for KLH-induced DTH model

References

  1. Janeway CA Jr., Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease, 2001. 5th Edition.

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