High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients

Abstract

Naive and central memory T lymphocytes (T_N and T_CM ) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of T_N and T_CM lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA-79). T_N and T_CM lymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm² ; interquartile range (IQR) = 0-6·39] and ileum of Crohn's disease patients (1·40; 0-4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEV^high ) was associated with increased infiltration of T_N and T_CM in the inflamed gut (median 87%; IQR = 82-93% of T cell population), compared to HEV^low patients (58%; 38-81%; P = 0·003). The number of colonic follicles was higher in HEV^high patients (median 0·54/mm² ; IQR 0·28-0·84) compared to HEV^low patients (0·25/mm² ; 0·08-0·45; P = 0·031) and controls (0·31/mm² ; 0·23-0·45; P = 0·043). Increased homing of T_N and T_CM lymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.