Delayed-type Hypersensitivity (DTH) Nonhuman Primates Disease Model

Understand Delayed Type Hypersensitivity (DTH), a cell-mediated immune response involving T cells and macrophages. Explore its causes, symptoms, and the advantages of using a non-human primate (NHP) model for research and development of new immunosuppressants and immunomodulators. Learn about study design, clinical endpoints, and key results demonstrating the effectiveness of treatment in reducing skin induration and inflammation.

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Product Introduction

Delayed type hypersensitivity (DTH), also called type IV hypersensitivity, is a common immune response that occurs through direct action of sensitized T cells when stimulated by contact with antigen. It is referred to as a delayed response in that it will usually require 12–24 hours at a minimum for signs of inflammation to occur locally.

Delayed type hypersensitivity (DTH)

Disease symptoms: skin rash, eczematoid reaction

Causes: in contrast to type I, II, III hypersensitivity, which mainly involves antibody response (humoral), DTH is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.

This reaction is caused when CD4+ Th1 cells recognize foreign antigen in a complex with the MHC class II on the surface of antigen-presenting cells, which stimulates the proliferation of CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma (IFN-γ), inducing the further release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

The overreaction of the helper T cells and overproduction of cytokines damage tissues, cause inflammation, and cell death.

Advantages of NHP DTH model

•Due to the high degree of similarity exists between the immune systems of human and non-human primate species, monkey models are of utmost value in evaluation the effects of interventional compounds for human immune system.

•The delayed-type hypersensitivity (DTH) in cynomolgus monkey is a low invasive and non-terminal model based on the induction of local cell-mediate immune response.

•Monkey DTH model is useful in pre-clinical development of new immunosuppressor/immunomodulator (IS/IM) agents for clinically relevant diseases.

•Cell-mediate immune response in monkey is also a useful model for evaluation of immunotoxicity, providing further insight on risk assessment of drug candidates