IL-10 and IL-2 Knockout Mice

Abstract

The colitis in IL-10 deficient mice is characterized by immune system dysregulation, in that regulatory T cells either fail to develop or are functionally impaired in the absence of IL-10. This leads to an IL-12 and IFN-γ directed excessive generation and activation of Th1 cells directed towards lumina] bacterial antigens and resultant immunopathology resembling human Crohn’s disease. Intestinal inflammation is dependent upon the presence of luminal microflora, and can be modulated through antibiotics, probiotics, and antibodies directed at proinflammatory cytokines. Disease is highly dependent upon genetic background. IL-2-deficient mice develop a progressive inflammatory bowel disease with similarities to human ulcerative colitis. IL-2-deficient mice initially have normal numbers of B and T lymphocytes; however, the lamina propria of inflamed colons in older mice contain elevated levels of CD4+ and CD8+ T cells, as well as B220+ B cells, suggesting that both T and B cells are spontaneously activated in the colonic immune response. As in the IL-10 deficient mouse, disease in the IL-2-deficient mouse is dependent upon the presence of luminal microflora and is modulated by the genetic background of the animal. Overall, findings in these two models of colitis suggest that genetically susceptible hosts can mount a pathogenic cellular immune response to specific nonpathogenic bacterial species as a consequence of defective immunologic tolerance.