The activation of naïve T cells results in their proliferation and differentiation into a particular T-helper (Th) phenotype, namely Th1, Th2 or Th17 cells. This thesis focuses on the role of pro-inflammatory Th1 and Th17 cells in the induction of autoimmune disease of the central nervous system (CNS), using murine experimental autoimmune encephalomyelitis (EAE) as the model. Classically, EAE has been considered to be a Th1-mediated disease. However, since the emergence of the Th17 cells, there has been a paradigm shift towards Th17 cells being the key pathogenic subset in autoimmune disease. This thesis established robust protocols for the differentiation of naïve T cells into myelin-reactive Th1 or Th17 cells, producing ‘clean’ populations devoid of any contaminating cells. Passive T cell-transfer experiments revealed that myelin-reactive Th1 cells could induce EAE, whereas Th17 cells could not. This lack of disease correlated with the inability of the Th17 cells to accumulate in the non-inflamed CNS. Myelin-reactive Th1 cells did have this capability and only once inflammation was established, could Th17 cells be identified in the CNS, potentially exacerbating the disease. After these differences were observed, the project investigated two main aims: 1) to identify differences in homing molecule expression on Th1 and Th17 cells which could explain the difference in their ability to home to the CNS, and to investigate the functional significance of such differences, by molecular blockade; 2) to investigate the requirements for three key cytokines in EAE pathogenesis in passive T cell transfer models, investigating IFN-γ,IL-17 and TNF-α. P-selectin glycoprotein ligand-1 appeared to be important for the initial entry of inflammatory T cells into the CNS. Th1 cells deficient in IFN-γ were capable of IFNinducing EAE. A proportion of the mice developed “atypical” clinical signs, which correlated with T cell infiltration predominantly of the brain, rather than the spinal cord. This atypical EAE may be IL-17 dependent. In conclusion, this thesis indicates the importance of not focusing all resources and therapeutic approaches on Th17- induced inflammation as Th17 cells may not play such a major role as previously thought.