IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: Roles of IL-6 in the activation and differentiation of autoreactive Tcell

Although autoreactive T cells recognizing self myelin Ags are present in mo st individuals, autoimmune disease of the central nervous system is a relat ively rare medical condition, Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a seco nd signal delivered by costimulatory molecules or cytokines, Although in vi tro studies have suggested that cytokines, especially proinflammatory cytok ines such as IL-l, IL-6, and TNF are involved in T cell activation, their p recise roles in vivo are not clear. To determine the roles of proinflammato ry cytokines in T cell activation in vivo and in the development of autoimm une disease, we have studied experimental autoimmune encephalomyelitis (EAE ) in mice deficient in IL-6, We found that Il-6-deficient mice were complet ely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal in flammation and demyelination in the central nervous system and deficiency i n neurologic functions. Furthermore, Ive established that the resistance to EAE in IL-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo , These results strongly suggest that IL-6 plays a crucial role in the acti vation and differentiation of autoreactive T cells in vivo and that blockin g IL-6 function can be an effective means to prevent EAE.