Innate and Specific Mucosal Immunity

A large mucosal immune system controlled by unique, organ-specific regulations operates alongside and separate from the peripheral or systemic immune system. This local immune system is seen as a major interface between the innate and the specific immune system. We have been interested in the immunopathogenesis of a chronic inflammatory bowel disease (IBD) developing in CD4+ T cell-transplanted, immunodeficient (SCID) mice. Microbial-derived factors drive (directly or indirectly) the activation, expansion and/or Th1 differentiation of adoptively transferred TCRαβ CD4+ T cells in the colonic lamina propria of transplanted, diseased SCID mice with colitis (the particular manifestation of IBD observed in this model). A TCR-independent, polyclonal stimulus seems to be the major stimulus for this cellular immune response in the colon. This suggests that T cells of the specific peripheral immune system that migrate into compartments of the mucosal micro-environment change their activation requirements and acquire responsiveness to stimuli that usually drive the innate immune system.