TCRγδ⁺CD8αβ⁺ T cell in health and disease: a novel and functionally active subpopulation of T-cells enriched within the gut

γδ T-cells have been implicated in the pathogenesis of immune-mediated diseases such asinflammatory bowel disease (IBD). However, a potential role of different immune cell subsets in IBD and also in the process of mucosal healing upon treatment is unknown. γδ T-cells have been divided into CD8αα⁺ and CD8^- T-cells. By using flow cytometry and RT-PCR, we described for the first time anovel subset of human γδ T-cells expressing CD8αβ heterodimers on their surface. We found thatthese TCRγδ⁺CD8αβ⁺ T-cell subset exist in both human peripheral blood as well as in the gut, however they were differentially enriched within the gut. TCRγδ⁺CD8αβ⁺ T-cells displayed highcytotoxic activity by expressing Fas Ligand on their surface and also producing Granzyme B and Perforin. We showed that these cells can produce INFγ and TNFα but they did not show the ability toproduce IL-17 in healthy individuals. In patients with IBD, we found a decrease in the percentage ofintestinal CD8αβ⁺ γδ T-cells compared to healthy controls. Moreover, the percentage of TCRγδ⁺CD8αβ⁺ T-cells out of γδ T-cells showed a negative correlation with Crohn's disease activity.Three months of anti-TNFα (adalimumab) therapy increased the percentage of TCRγδ⁺CD8αβ⁺ T-cellsclose to the level of healthy controls. These results suggest that TCRγδ⁺CD8αβ⁺ T-cells might possiblyplay a role in gut inflammation and also intestinal wound healing after anti-TNFα treatment. These results are likely to have implications for the development of novel therapies to treat mucosal inflammatory diseases.