responses during autoimmunity, we investigated the role of Nur77 in modulation of human and murine T cell responses in vitro and characterised autoreactive T cell responses in vivo making use of the animal model of Multiple Sclerosis (MS), i.e. experimental autoimmune encephalomyelitis (EAE). We observed that Nur77 was expressed within hours after T cell receptor triggering. Upon T cell receptormediated activation, Nur77-deficient T cells proliferated stronger than wildtype T cells and exhibited increased potential to differentiate into pathogenic TH1 and TH17 cells — both, in an antigen-independent setting and upon antigen-specific activation. Also in vivo, antigenspecific T cell activation by Nur77-competent dendritic cells resulted in enhanced proliferation and cytokine production when T cells lacked Nur77. After induction of EAE, Nur77-deficient animals exhibited an earlier onset of disease and a significantly aggravated clinical score, which was accompanied by enhanced MOG35–55-specific TH1 and TH17 cell responses both in the periphery and within the CNS. Importantly, also the transfer of MOG35–55-specific Nur77-deficient T cells into healthy wildtype recipients induced a more aggravated EAE disease course than transfer of MOG35–55-specific wildtype T cells, which further demonstrated the importance of Nur77 for restriction of pathogenic T cell responses. In human T cells we observed dysregulated Nur77 expression after TCR triggering when T cells were derived from MS patients, thus indicating that Nur77 could also be important for control of human autoreactive T cell responses. Taken together, Nur77 limits T cell responses in the context of CNS autoimmunity by restricting T cell proliferation and differentiation into TH1 and TH17 effector cells. Hence, Nur77 dysregulation might contribute to enhanced T cell activation in T cell-mediated autoimmune diseases such as MS.