CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease

gamma delta T cells have been attributed a wide variety of functions, which in some cases may appear as contradictory. To better understand the enigmatic biology of gamma delta T cells it is crucial to define the constituting subpopulations. gamma delta T cells have previously been categorized into two subpopulations: CD8 alpha alpha(+) and CD8-cells. In this study we have defined and characterized a novel subset of human gamma delta T-cells expressing CD8 alpha beta. These CD8 alpha beta(+) gamma delta T cells differed from the previously described gamma delta T cell subsets in several aspects, including the degree of enrichment within the gut mucosa, the activation status in blood, the type of TCR delta variant used in blood, and small but significant differences in their response to IL-2 stimulation. Furthermore, the novel subset expressed cytotoxic mediators and CD69, and produced IFN-gamma and TNF-alpha. In patients with active inflammatory bowel disease the mucosal frequencies of CD8 alpha beta(+) gd T cells were significantly lower as compared with healthy controls, correlated negatively with the degree of disease activity, and increased to normal levels as a result of anti-TNF-alpha therapy. In conclusion, our results demonstrate that CD8 alpha beta(+) gamma delta T cells constitute a novel lymphocyte subset, which is strongly enriched within the gut and may play an important role in gut homeostasis and mucosal healing in inflammatory bowel disease.