P007 Identification and characterisation of intestine-derived circulating resident memory T cells (ex-Trm) in health and Inflammatory Bowel Disease

Rodger, B.(1);Hoti, I.(1);Gordon, H.(1);Lindsay, J.(1);Stagg, A.(1);

(1)Blizard Institute- Queen Mary University of London, Centre for Immunobiology, London, United Kingdom


Tissue resident memory T cells (Trm) persist in peripheral tissues where they protect against pathogens but can also contribute to inflammatory disease. Recent work shows that Trm can re-enter the circulation and give rise to new effector T cell and Trm populations in secondary tissue sites. Such ‘ex -Trm’ derived from the skin co-express the residency marker CD103 with cutaneous leukocyte antigen (CLA), a marker associated with skin tropism. Many T cells in the human intestine are Trm but it is unknown whether these cells re-enter the circulation; the existence of gut-derived ex-Trm would have important implications for IBD treatment targeting the recruitment of circulating gut-homing cells. Here, we identify a population of blood cells that co-express CD103 and the gut-homing integrin a4b7 and determine how they are changed in IBD.


Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and patients with active IBD (Crohn’s disease or ulcerative colitis). Cell surface staining and multi-colour flow cytometry were used to identify CD4+ and CD8+ subsets of antigen experienced (CD45RA-) conventional T cells (abTCR+) and determine expression of markers associated with tissue tropism and residency.


Staining with antibodies to CD103 and b7 integrin were used to define CD103b7+a4b7+ putative gut ex-Trm based on the excess per cell expression of b7 resulting from its contribution to both integrins. A separate CD103b7+a4b7- population defined by 1:1 expression of CD103 and b7 contained CLA+ skin ex-Trm. Gut ex-Trm comprised 0.3% total circulating CD8+ T cells (range 0.02–1.4%), and 1.2% CD4+ T cells (range 0.3–3%). Gut and skin ex-Trm were phenotypically similar; both expressed the residency associated markers CD101 and CD9 but lacked expression of CD69. Gut ex-Trm were phenotypically distinct from both traditional CD103-a4b7+ gut tropic CD45RA- antigen-experienced T cells and naïve T cells; significantly more gut ex-Trm expressed CD101 and CD9 and fewer expressed CD27. The proportion of gut ex-Trm did not differ between heath and IBD. However, the ratio of gut:skin ex Trm was significantly reduced in active Crohn’s disease but not ulcerative colitis indicating a selective reduction in the population derived from the intestine.


A putative population of gut-derived ex-Trm can be identified in the blood of healthy controls and IBD patients. This population has a distinctive phenotype similar to that of previously described skin-derived ex-Trm. Circulating ex-Trm could link discreet areas of intestinal inflammation in Crohn’s disease and there is a selective loss of the gut ex-Trm population from the blood of these patients. The role of ex-Trm in IBD merits further study.