Abstract Autoimmune diseases such as type I diabetes (TID) and multiple sclerosis (MS) are chronic conditions that have a significant impact on quality of life. CD8+ T-cells play an important role in the pathogenesis of these diseases. However, drugs that target the entire CD8+ T-cell population are not desirable because this population provides protection against infection. Accordingly, there is an urgent requirement to develop novel treatment strategies that exclusively target the autoreactive CD8+ T-cell population. CD8+ T-cells express a molecule called CD8 at their cell surface which assists with activation. We have demonstrated that autoreactive CD8+ T-cells are entirely dependent on CD8 for activation. In stark contrast, pathogen specific CD8+ T-cells are characterized by higher functional sensitivity and are relatively CD8 independent. This represents an intrinsic difference that can be exploited for therapeutic benefit. Our data suggests that “blocking anti-CD8 antibodies” can be used to block autoreactive CD8+ T-cell attack without affecting pathogen specific immunity, a key goal in the treatment of autoimmunity. The generation of “blocking anti-CD8 antibodies” offers an opportunity to develop a novel therapeutic approach that can be used to treat CD8+ T-cell mediated autoimmunity. In order to conduct a further assessment, we are currently developing a strategy for in vivo validation of the approach.