title: Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease.
abstract: BACKGROUND
  FOXP3+ regulatory T cells (Tregs) are critical for preventing intestinal inflammation. However, FOXP3+ T cells are paradoxically increased in the intestines of patients with the inflammatory bowel disease (IBD) ulcerative colitis (UC) or Crohn's disease (CD). We determined whether these FOXP3+ cells in IBD patients share or lack the phenotype of such cells from patients without IBD.
  
  
  METHODS
  We quantified and characterized FOXP3+ Treg populations, as well as FOXP3- CD4+ T cells, in the lamina propria lymphocytes (LPL) of intestine surgically resected from patients with and without IBD, and in the blood of controls or Crohn's patients with or without disease activity.
  
  
  RESULTS
  In all samples, a similar fraction of FOXP3+ cells expressed the "natural" Treg (nTreg) marker Helios, suggesting that, in IBD, these cells are not entirely "induced" Tregs (iTregs) derived from activated effector T cells. Helios+ and Helios- FOXP3+ T cells demonstrated similar expression of maturation markers, activation markers, and inhibitory molecules between IBD patients and controls, while FOXP3- cells paradoxically expressed more of the inhibitory receptors CD39, CTLA4, and PD-1 in inflamed mucosa. Greater expression of activation markers was also seen in both Helios+ and Helios- Tregs, relative to FOXP3- cells, in both IBD patients and controls, indicating that Tregs are effectively activated by antigen in IBD.
  
  
  CONCLUSIONS
  Extensive immunophenotyping revealed that Helios+ and Helios- mucosal Tregs exist at a similar frequency, and have a similar expression of inhibitory molecules and activation markers in patients with IBD as in healthy controls.
authors: Translational Research Program at the Benaroya Research Institute at Virginia Mason, Seattle Washington, United States of America.
authors: James D
authors: JD
authors: Lord
authors: Translational Research Program at the Benaroya Research Institute at Virginia Mason, Seattle Washington, United States of America.
authors: Donna M
authors: DM
authors: Shows
authors: Translational Research Program at the Benaroya Research Institute at Virginia Mason, Seattle Washington, United States of America.
authors: Janice
authors: J
authors: Chen
authors: Department of Surgery, Virginia Mason Medical Center, Seattle, Washington, United States of America.
authors: Richard C
authors: RC
authors: Thirlby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000276:immunology*; D007413:Intestinal Mucosa / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D011971:Receptors, Immunologic