| As the most potent antigen-presenting cell of the immune system, the dendritic cell has the unique capacity to both initiate and regulate antigen-specific immune responses. In the normally functioning immune system, the combination of costimulatory molecules and cytokines presented with MHC-peptide complexes on dendritic cells determine the penultimate function of naive antigen-specific T cells. Thus, scientist's have great interest in the function of dendritic cells in autoimmune disease, where self-reactive T cells are activated in the periphery and regulation of this response is deficient. This study demonstrates abnormalities of dendritic cell subsets within secondary lymphoid tissues of the autoimmune-prone NOD mouse and demonstrates a genetic basis for abnormalities of these cells in vivo. Studies where hematopoeitic progenitors were cultured with GM-CSF and IL-4 showed that NOD stem cells have a limited capacity to differentiate to fully mature dendritic cells. Analysis of several congenic mouse strains have identified this as a genetically controlled phenomenon, and further indicates potential in vivo differentiation and functional abnormalities that may lead to a dysfunctional immune system. Finally, activation of a lymphoid cell population known to interact with dendritic cells, the NK-T cell, is capable of limiting pancreatic beta cell destruction, apparently by initiating the emigration of dendritic cells from the pancreas to the draining lymph node, thus decreasing islet inflammation. Together, these findings establish a crucial role for abnormal dendritic cell development in the initiation and resolution of beta cell destruction in Type I diabetes. |
