Imaging Immunity: T-Cell Distribution and Density in Inflammatory Bowel Diseases
PET scans help researchers observe where inflammation arises after inducing colitis in mice
About 3 million Americans suffer from an inflammatory bowel disease such as Crohn’s or ulcerative colitis. Except for patient self-reporting of symptoms, the methods used to assess the disease are highly invasive: colonoscopy and biopsy. Now a team of researchers at the University of California, Los Angeles led by Anna Wu reports on a noninvasive test in a mouse model using positron emission tomography to ascertain the number and distribution of immune system T-cells in the bowel as a diagnostic tool and an indication of disease severity. The researchers published their results in the June issue of the Journal of Nuclear Medicine.
The team induced colitis in mice by dissolving dextran sulfate sodium in their drinking water for five days and then injecting the mice with an engineered antibody tagged with zirconium-89 as a tracer. The targets of the antibody were CD4+ T-cells, which protect against infection and are known to mediate inflammation in the gut. In inflammatory bowel disease, these cells are thought to mistake normal gut microbiota for invasive pathogens.
After a week the mice showed strong signs of IBD: weight loss, loose stool and bleeding. Tissue examination showed the mice’s colons were shorter and heavier than those of the control mice. They had also lost epithelial cells and their intestinal mucosa had been infiltrated by inflammatory cells. PET scans then revealed where the CD4+ T-cells traveled in the mice’s intestines. Their numbers had increased markedly in the bowel, and lymph nodes around the colon were dramatically enlarged.
The researchers suggest that this immuno-PET assay of CD4+ T-cells will enhance investigation of inflammatory diseases in animal models and eventually provide a noninvasive way to determine the severity and extent of inflammation, pinpoint the location of inflammation, and reveal which subsets of T-cells are involved in the human versions of the diseases.