Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish.

Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standards. One of the several factors involved in this question may be reduced exposure to the immunomodulatory effects of parasitic helminths. Several investigations on treatment of mice and humans with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis-inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co-injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48 hours post-exposure). Gene expression studies of TNBS-treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate-driven immune response was seen in both TNBS and TNBS + ES groups, but expression values were significantly depressed for several important pro-inflammatory genes in the TNBS + ES group, indicating protective mechanisms of Anisakis ES compounds on intestinal immunopathology in zebrafish.

Characteristics of rat CD4(+)CD25(+) T cells and their ability to prevent not only diabetes but also insulitis in an adoptive transfer model in BB rats.

Human and mouse CD4(+)CD25(+) T cells have been intensively studied through the last decade. However, little is known about this subset in other species. This study describes the phenotype of rat CD4(+)CD25(+) Foxp3(+) T cells and the site in which they exert regulation in a transfer-induced autoimmune diabetes model. Several proteins and mRNAs are up-regulated in unstimulated rat CD4(+)CD25(+) T cells compared with CD4(+)CD25(-) T cells, including Foxp3, Lag-3, CD80, interleukin 10 (IL-10) and CTLA-4. To investigate CD4(+)CD25(+) T cells in vivo, we transferred three million diabetogenic T cells either alone or in combination with two million CD4(+)CD25(+) T cells to 30-day-old BB rats. The pancreas and the pancreatic lymph nodes were examined as two potential regulatory sites. Time-course analysis of pancreatic histology following diabetogenic T-cell transfers revealed insulitis from about 14 days after transfer. By contrast, rats receiving both diabetogenic T cells and CD4(+)CD25(+) T cells had no insulitis at any time. Moreover, the frequency of diabetogenic T cells in the pancreatic lymph nodes 2 days after transfer was significantly reduced in rats receiving both subsets. These data indicate that the primary site of T-cell regulation is in the draining lymph nodes and not the pancreas in our model.