V 2+T Cell expansion in crohn's disease: impact of inflammation, disease activity and treatment

Introduction Crohn's disease (CD) is driven by inappropriate inflammatory responses to gut microbiota. Circulating, microbe-responsive Vγ9Vδ2+(δ2)T cells express 'gut-homing' integrin β7 and may contribute to intestinal inflammation. Hypothesis Increased intestinal permeability and microbe exposure in CD leads to activation and expansion of δ2T cells. Aim To compare δ2T cells in CD patients, unaffected siblings and healthy controls (HC). Methods Flow cytometry was used to gate T cell subsets in 36 CD patients, 13 siblings and 13 HC. δ2T cell activation and cytokine production in culture of HC and CD peripheral blood mononuclear cells (PBMCs) was assayed upon stimulation with synthetic microbial phosphoantigen (HDMAPP) in vitro. Results When HC and CD PBMCs were activated by HDMAPP, δ2T cells proliferated, produced high levels of IFNγ and TNFα, and maintained high integrin β7 levels in vitro. In CD patients, the variation in numbers of circulating δ2T cells was significantly (p=0.02) greater than in HC (0.1-138.4 vs 6.2-37.8 cells per μl blood; 0.1-13.0% vs 0.5-2.9% of total T cells). Of the 19 CD patients not treated with thiopurines (TP), 9 had expanded δ2T cells (number or proportion above upper limit of HC) and of these, 8 (89%) had inactive disease (HBI