Dataset Information

T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.

ABSTRACT: 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.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.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.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.

SUBMITTER: Lord J

PROVIDER: S-EPMC4526221 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.

Lord James J Chen Janice J Thirlby Richard C RC Sherwood Anna M AM Carlson Christopher S CS

Inflammatory bowel diseases 20150101 1

<h4>Background</h4>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.<h4>Methods</h4>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 a ...[more]

PMID: 25437819

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Project description:We aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases.We retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral load.At baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA- patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA- patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000-36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157-5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral loads.Aging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.

Dataset Information

T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.

Publications

T-cell receptor sequencing reveals the clonal diversity and overlap of colonic effector and FOXP3+ T cells in ulcerative colitis.

Similar Datasets

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