Delayed-type hypersensitivity (DTH) Mouse Model
The Delayed-type hypersensitivity (DTH) Mouse Model helps you quickly assess the efficacy of immunomodulatory or immunosuppressive compounds
Delayed-type hypersensitivity (DTH) reactions, also known as type IV hypersensitivity reactions, are local inflammatory reactions mediated by cell-associated antigens involving CD4+ or CD8+ T-cell activation. During the afferent phase of DTH, mice are typically immunized by subcutaneous injection with a specific hapten or antigen emulsified with an adjuvant. The efferent phase is typically initiated 5-12 days after sensitization, via antigen challenge by subcutaneous footpad or intradermal ear injection.
The delayed-type hypersensitivity (DTH) mouse model represents a relatively quick and useful approach for evaluating the efficacy of potential immunomodulatory or immunosuppressive compounds to modulate the cellular immune response, primarily Th1 and Th17 type responses. By challenging the cell-mediated immune response, you can obtain valuable information such as whether your lead immunomodulatory compound can reduce DTH in mice. Hypersensitivity reactions can be categorized based on the delivery of the antigen through subcutaneous injection, topical administration or via the gut.
Developing new, safe and efficacious therapies is an extremely intricate process. As a preclinical immunology contract research organisation (CRO), InnoSer partners with you to help you navigate the complexities of this research area.
Take advantage of InnoSer’s collaborative approach to develop the most optimal study design. With flexible and fast study start times you can perform your research at an accelerated pace. By outsourcing your preclinical oncology studies to InnoSer, you gain access to our in vitro and in vivo immunology drug development portfolio.
Delayed-type hypersensitivity (DTH) Mouse Model characteristics:
- DTH can be evaluated in wild-type (i.e., C57BL6) or humanized mice carrying human transgenes.
- DTH can be induced by antigen injection (OXA, KLH), skin absorption (DNFβ) following topical administration or via the gut (DSS-induced colitis).
- Complementary in vitro immuno-assays, histopathology analyses and PK/PD profiling services.
Key readouts in the delayed-type hypersensitivity (DTH) mouse model:
Test the efficacy of your treatments in the DTH mouse model with the following readouts:
- Localized ear swelling measurement
- Blood and/or serum collection for PK/PD profiling and/or immune cell profiling via flow cytometry
- Histopathological evaluation using either classical H&E stains and/or IHC
- Inflammatory cytokines MSD and ELISA
Example data featuring the delayed-type hypersensitivity (DTH) mouse model:
The delayed-type hypersensitivity (DTH) mouse model represents a relatively quick and useful approach for evaluating the efficacy of potential immunomodulatory or immunosuppressive compounds.
On day 0, mice were sensitized by a subcutaneous injection with KLH/CFA/IFA emulsion in the tail base. Six days later, following baseline measurements, mice were challenged with a KLH injection into one ear and PBS injection into the other ear as a within-subject control. Treatment with an anti-inflammatory drug (Rapidexon) was used as a positive control for KLH hypersensitivity.
We observed clear increases in ear thickness on the days after KLH challenge compared to baseline (day 6). Moreover, ear thickness of PBS control ears and KLH-injected ears of Rapidexon-treated animals showed reduced swelling throughout the whole study duration, confirming the suitability of this assay. Data is shown as mean±SEM.
The delayed-type hypersensitivity (DTH) mouse model represents a relatively quick and useful approach for evaluating the efficacy of potential immunomodulatory or immunosuppressive compounds.
Mice were sensitized with 0.5% DNFB on abdominal skin on day 0 and elicited on both ears with 0.5% DNFB on day 5. Ear thickness was measured daily from day 5 to day 10. The graph shows that treatment with Rapidexon (green) significantly reduced ear thickness compared to the PBS control (red), indicating the anti-inflammatory efficacy of Rapidexon in this contact dermatitis model. Data are presented as mean ± SEM.
The delayed-type hypersensitivity (DTH) mouse model represents a relatively quick and useful approach for evaluating the efficacy of potential immunomodulatory or immunosuppressive compounds.
All efficacy studies can be complemented with histopathology readouts with in-house expert pathologist evaluation. As an example, the H&E-stained digitalized whole-slide images below show (A) infiltration of immune cells consisting of mainly lymphocyte in the dermis. (B) Non-inflamed dermis.
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