T1217 A Novel Population of CD56+ HLA-DR+ Colonic Lamina Propria Cells Is Associated with Inflammation in Ulcerative Colitis

Abstract

INTRODUCTION: The immunopathology of ulcerative colitis (UC) relates to an inappropriate mucosal immune response to constituents of the intestinal microbiota in genetically susceptible individuals. HLA-DR+ lin-/dim (lin = anti-CD3,14,16,19,34) cells extracted from human intestinal tissue contain CD11c+ myeloid dendritic cells (DC) that contribute to the immunoregulatory events that normally limit inflammatory responses to commensal bacteria. Also present within the HLA-DR+ lin-/dim population are hitherto poorly characterized CD11ccells. We hypothesized that this population in the gut may also contribute to intestinal inflammation in active UC AIMS & METHODS: HLA-DR+ lin-/dim cells were identified in freshly isolated lamina propria mononuclear cells by multicolour flow cytometry, from patients with UC (n=48) and controls (n=22). The proportion and number of CD11c+ and CD11ccells within this population were determined. Surface expression of the activation/maturation markers CD40, CD86, Toll-like receptors (TLR), TLR-2, TLR-4, and the natural killer cell marker, CD56 was assessed on each cell population. Morphology was assessed by electron microscopy and T cell stimulatory capacity measured in allogenic mixed leucocyte reaction (MLR). RESULTS: Lamina propria colonic HLA-DR+ lin-/dim cells, of the CD11c-, but not the CD11c+ subset, were significantly increased in inflamed tissue of patients with UC compared with control tissue (UC 447±94 versus Control 104±17 per mg; p<0.001). Numbers of CD11cHLA-DR+ lin-/dim cells decreased after resolution of macroscopic inflammation. Nonetheless, CD11cHLA-DR+ lin-/dim cells were significantly increased in non-inflamed tissue of UC patients compared with colonic tissue from healthy subjects (p<0.05). In UC, these CD11ccells expressed CD40, CD86, TLR-2 and TLR-4 at lower levels than on their CD11c+ counterparts and were weakly stimulatory in an MLR. Few CD11cHLA-DR+ lin-/dim colonic cells expressed markers associated with blood CD11cHLA-DR+ lin-/dim plasmacytoid DC (BDCA2, BDCA4 and high levels of CD123) but a major subset expressed high levels of the Natural Killer (NK)marker CD56. CONCLUSION: Intestinal inflammation in UC is associated with the presence of a population of cells that share phenotypic features of both antigen presenting cells and NK cells. This novel population of human colonic cells may function in immune regulation or tissue repair. In addition, their increased presence in quiescent UCmay be amarker of sub-clinical inflammatory activity