The pathogenicity of IL-17+ CD8+ T cells has been mainly investigated using transgenic mouse models. Using the OT-I transgenic model, antigen-specific IL-17+ CD8+ T cells treated with IL-23 were found to be diabetogenic when adoptively transferred into RIP-mOVA mice. The pathogenicity was diminished upon treatment with anti-IL-17A and anti-IL-17F antibodies, indicating that IL-17 is essential for disease development . Furthermore, in EAE mice myelin oligodendrocyte glycoprotein-specific CD8+ T cells isolated from the lymph nodes and central nervous system at the peak of disease were found to express IL-17 ex vivo (after PMA and ionomycin stimulation). These cells did not express granzyme B, indicating their potential pathogenicity was not dependent on a cytotoxic mechanism and may be related to pro-inflammatory cytokine production . As previously mentioned, healthy individuals carrying the protective R381Q variant in the IL23R locus had a lower IL-17+ CD8+ T cell frequency in peripheral blood compared to those who did not carry the variant . Since carriage of this variant (or others in high linkage disequilibrium with R381Q) confers decreased susceptibility to immune mediated diseases such as inflammatory bowel disease, ankylosing spondylitis and psoriasis , , , this indicates a potential unidentified role of IL-17+ CD8+ T cells in the pathogenesis of these diseases. In the context of psoriatic arthritis, CD8+ IL-17+ T cells frequencies were increased in the synovial fluid compared to peripheral blood, correlated with several clinical parameters of disease and were associated with erosive disease, suggesting these cells may play a role in the pathogenesis of this disease .