Following antigen-specific responses within dextran sodium sulfate colitis: Tools for drug research

The interest in the role of T helper cells in the initiation and progression of inflammatory bowel disease (IBD) has increased as a result of the apparent importance of Th17 cells in IBD pathogenesis. The dextran sodium sulfate (DSS) model of colitis recruits many T lymphocytes to the site of inflammation and very little is known about the subtype (Th1, Th2, Th17 and Treg) and antigen-specificity of these T cells. The subtype of the gutinfiltrating T helper cells is a result of the current gut environment during the initiation of inflammation and its ability to direct antigen presenting cell maturation via pathogen recognition receptors. Detecting gut antigen-directed T cells in DSS colitis and many other murine colitis models is hampered by the lack of known antigens within the gut at the time of inflammation. Therefore, DSS administration was combined with the administration of the tracker antigen; ovalbumin. As expected, ovalbumin administration did not change the clinical phenotype of the disease as determined by weight and colon length. However, ex vivo stimulation of lymphocytes with ovalbumin showed a clear population of antigenspecific CD4+Foxp3- T helper cells in the spleens of colitic mice indicating that the administered ovalbumin was presented by gut-resident antigen presenting cells. Analysis of T cell transcription factors using semi-quantitative RT-PCR revealed that RORγT, Foxp3, Tbet and GATA3 were all expressed in the lamina propria of colitic mice and their expression did not change as a result of ovalbumin administration, indicating that ovalbumin administration does not skew the T cell response. These results demonstrate that not only does DSS administration break tolerance against orally administered neo-antigens, but that ovalbumin may be used as a tracker antigen within the DSS model. This newly developed model will ultimately help elucidate how the gut environment and pathogen-associated molecular patterns steer the development of adaptive immune responses during colitis.