Customized T Cell Transfer Models of IBD

In inflammatory bowel disease (IBD), CD4⁺T cells are overactivated and produce excessive proinflammatory cytokines that contribute to the development of intestinal inflammation. In 1990, a novel method using a T cell transfer system was introduced, which contributed tremendously to the accumulation of knowledge about regulatory T cells. Adaptive transfer of CD4⁺CD45RB^high T cells (naive T cells) from healthy wild-type (WT) mice into syngeneic recipients that lack T and B cells induces a pancolitis and small bowel inflammation at 5-8 weeks following T cell transfer. The advantage of the T cell transfer model of colitis is that the onset and severity of the disease are more closely synchronized than in other models. In addition, T cell transfer models of IBD are much more relevant to human disease than the erosive, self-limiting models of acute colitis.

Fig. 1. The cell transfer colitis model. (Kiesler et al., 2015)

Our CD4⁺CD45RB^high T Cell Transfer Model of Colitis

Ace Therapeutics is a leading global preclinical contract research provider offering customized CD4⁺CD45RB^high T cell transfer models of colitis to accelerate clients' preclinical IBD studies, including:

• Dissect the importance of T cells in regulating intestinal homeostasis and inflammation, but also analyze the distinct features and functions of different T cell subsets in colitis.
• Discover the translational and therapeutic implications of genetically modified T cell subsets in colitis.
• Test drugs in preventing and treating intestinal inflammation.
• Investigate the interactions among T cells, innate cells, and microbiota.

Procedures for Establishing a CD4⁺CD45RB^high T Cell Transfer Model of Colitis

Adoptive transfer of naive T cells (CD4⁺CD45RB^high) into immune deficient Rag -/- mice. It usually takes around 6–8 weeks, depending on the microbial populations present in the animal facility, to develop severe disease manifested by hunching, progressive weight loss, and diarrhoea.

Fig. 2. Assay workflow of CD4⁺CD45RB^high T cell adoptive transfer model of colitis.

Monitoring Disease Progression and Assessment of Colitis

• Weigh monitoring. During the first three weeks, each mouse is weighed weekly using a balance to monitor disease progression. Starting from week 4 to 5, recipient mice will begin to show symptoms of the disease and will be weighed twice a week.
• Clinical signs. Animals will be monitored daily for clinical signs (including weight loss, loose stools, and clinical scores) from week 3 through the end of the experiment. A scoring system is used, and both raw and analyzed data are available.
• Colon length. Colon is taken for weighing and length measurement.
• Histopathological analysis. Colon tissue is paraffin embedded, sectioned and stained with hematoxylin and eosin (H&E). Sections will be scored by our histopathologist based on a semi-quantitative scoring system.

Preclinical Evaluation in CD4⁺CD45RB^high T Cell Transfer Model of Colitis

• PK/PD blood collection
• Cytokine/chemokine analysis via Luminex(R)
• ELISA
• Clinical chemistry analysis
• Soft tissue collection
• Histopathologic analysis
• Immunohistochemistry analysis
• Endoscopy
• Flow cytometry analysis

Ace Therapeutics' team of experts has many years of experience providing the CD4⁺CD45RB^high T cell transfer model of colitis for biotech and pharmaceutical companies. This model allows us to help clients investigate the specific immunological mechanisms responsible for induction and discover multiple drug targets that work via modulation of T cell-mediated cytokines. Please contact us to discuss your IBD research needs.