title: T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.
abstract: BACKGROUND
  FOXP3 regulatory T cell prevent inflammation but are paradoxically increased in ulcerative colitis (UC). Local T-cell activation has been hypothesized to account for increased FOXP3 expression in colon lamina propria (LP) T cells.
  
  
  METHODS
  To see if human FOXP3 LP T cells are an activated fraction of otherwise FOXP3 effector T cells and explore their clonal diversity in health and disease, we deep sequenced clonally unique T-cell receptor hypervariable regions of FOXP3 and FOXP3CD4 T-cell subpopulations from inflamed versus noninflamed colon LP or mesenteric lymph nodes of patients with or without UC.
  
  
  RESULTS
  The clonal diversity of each LP T-cell population was not different between patients with versus without UC. Repertoire overlap was only seen between a minority of FOXP3 and FOXP3 cells, including recently activated CD38 cells and Th17-like CD161 effector T cells, but this repertoire overlap was not different between patients with versus without UC and was no larger than the overlap between Helios and Helios FOXP3 cells.
  
  
  CONCLUSIONS
  Thus, at steady state, only a minority of FOXP3, and particularly Helios, T cells share a T-cell receptor sequence with FOXP3 effector populations in the colon LP, even in UC, revealing distinct clonal origins for LP regulatory T cell and effector T cells in humans.
authors.affiliation: *Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA; Departments of †Gastroenterology and ‡Surgery, Virginia Mason Medical Center, Seattle, WA; §Adaptive Biotechnologies, Seattle, WA; and ‖Public Helath Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: James
authors.initials: J
authors.lastname: Lord
authors.forename: Janice
authors.initials: J
authors.lastname: Chen
authors.forename: Richard C
authors.initials: RC
authors.lastname: Thirlby
authors.forename: Anna M
authors.initials: AM
authors.lastname: Sherwood
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta