Experimental autoimmune encephalomyelitis in NF-kappa B-deficient mice: Roles of NF-kappa B in the activation and differentiation of autoreactive T cells

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS, which has long been used as an animal model for human multiple sclerosis, Development of autoimmune disease requires coordinated expressio n of a number of genes that are involved in the activation and effector fun ctions of inflammatory cells, These include genes that encode costimulatory molecules, cytokines, chemokines, and adhesion molecules. Activation of th ese genes is regulated at the transcriptional level by several families of transcription factors. One of these is the NF-kappa B family, which is pres ent in a variety of cell types and becomes highly activated at sites of inf lammation. To test the roles of NF-kappa B in the development of autoimmune diseases, we studied EAE in mice deficient in one of the NF-kappa B isofor ms, i.e., NF-kappa B1 (p50). We found that NF-kappa B1-deficient mice were significantly resistant to EAE induced by myelin oligodendrocyte glycoprote in. The resistance was primarily evidenced by a decrease in disease inciden ce, clinical score, and the degree of CNS inflammation. Furthermore, we est ablished that the resistance to EAE in NF-kappa B1-deficient mice was assoc iated with a deficiency of myelin oligodendrocyte glycoprotein-specific T c ells to differentiate into either Th1- or Th2-type effector cells in vivo. These results strongly suggest that NF-kappa B1 plays crucial roles in the activation and differentiation of autoreactive T cells in vivo and that blo cking NF-kappa B function can be an effective means to prevent autoimmune e ncephalomyelitis.