CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases

OBJECTIVE: Dendritic cells (DC) are the only antigen-presenting cells that can activate naive T lymphocytes and initiate a primary immune response. Th ey are also thought to have a role in immune tolerance. DC traffic from the blood to peripheral tissue where they become activated. They then present antigen and the costimulating signals necessary to initiate an immune respo nse. In this study, we investigated the number, subsets, and activation pat tern of circulating and intestinal DC from patients with clinically mild ul cerative colitis (UC) or Crohn's disease. METHODS: Patients were recruited, if they were not taking immunosuppressive therapy, and were assessed for clinical severity of their disease using fo r UC, the Clinical Activity Index, and for Crohn's disease, the Crohn's Dis ease Activity Index. Blood CD11c(+) and CD11c(-) DC subsets, expression of costimulatory antigens, CD86 and CD40, and the early differentiation/activa tion antigen, CMRF44, were enumerated by multicolor flow cytometry of linea ge negative (lin(-) = CD3(-), CD19(-), CD14(-), CD16(-)) HLA-DR+ DC. These data were compared with age-matched healthy and the disease control groups of chronic noninflammatory GI diseases (cGI), acute noninflammatory GI dise ases (aGI), and chronic non-GI inflammation (non-GI). In addition, cryostat sections of colonoscopic biopsies from healthy control patients and inflam ed versus noninflamed gut mucosa of inflammatory bowel disease (IBD) patien ts were examined for CD86(+) and CD40(+)lin(-) cells. RESULTS: Twenty-one Crohn's disease and 25 UC patients, with mean Crohn's D isease Activity Index of 98 and Clinical Activity Index of 3.1, and 56 heal thy controls, five cGI, five aGI, and six non-GI were studied. CD11c(+) and CD11c(-) DC subsets did not differ significantly between Crohn's, UC, and healthy control groups. Expression of CD86 and CD40 on freshly isolated blo od DC from Crohn's patients appeared higher (16.6%, 31%) and was significan tly higher in UC (26.6%, 46.3%) versus healthy controls (5.5%, 25%) (p = 0. 004, p = 0.012) and non-GI controls (10.2%, 22.8%) (p = 0.012, p = 0.008), but not versus cGI or aGI controls. CD86(+) and CD40(+) DC were also presen t in inflamed colonic and ileal mucosa from UC and Crohn's patients but not in noninflamed IBD mucosa or normal mucosa. Expression of the CMRF44 antig en was low on freshly isolated DC, but it was upregulated after 24-h cultur e on DC from all groups, although significantly less so on DC from UC versu s Crohn's or healthy controls (p = 0.024). The CMRF44(+) antigen was mainly associated with CD11c(+) DC, and in UC was inversely related to the Clinic al Activity Index (r = -0.69, p = 0.0002). CONCLUSIONS: There is upregulation of costimulatory molecules on blood DC e ven in very mild IBD but surprisingly, there is divergent expression of the differentiation/activation CMRF44 antigen. Upregulation of costimulatory m olecules and divergent expression of CMRF44 in blood DC was also apparent i n cGI and aGI but not in non-GI or healthy controls, whereas intestinal CD8 6(+) and CD40(+) DC were found only in inflamed mucosa from IBD patients. P ersistent or distorted activation of blood DC or divergent regulation of co stimulatory and activation antigens may have important implications for gut mucosal immunity and inflammation. (Am J Gastroenterol 2001;96:2946-2956. (C) 2001 by Am. Coll. of Gastroenterology).