Multiple sclerosis (MS) is a demyelinating disease caused by auto-antigen recognizing CD4 + T cells. However, IL-17A-producing CD4 + T cells that are bystander-activated by IL-1β and IL-23, and T cell receptors independently, could contribute to experimental autoimmune encephalomyelitis. Here, we studied the differences in the frequency and function of bystander-activated CD4 + T cells in patients with MS. A significantly higher frequency of CD4 + IL-1Rl + T cells was found in memory than in naïve CD4 + T cells and in Th17/Th17.1 than in Th1/Th2 subtypes in both MS and healthy controls (HC). Following IL-1β and IL-23 stimulation, IL-1Rl expression was markedly increased in both memory and Th17/Th17.1 cells, and their IL-17A-production was increased after bystander-activation, which was significantly higher in MS compared with HC. Our study suggests a potential role of IL-17A-producing bystander-activated CD4 + IL-1Rl + T cells in MS.