Peripheral and intestinal CD4+ T cells with a regulatory phenotype in pediatric patients with inflammatory bowel disease

Raffaella La Scaleia, Stefania Morrone, Antonella Stoppacciaro, Stefania Scarpino, Manila Antonelli, Elettra Bianchi, Giovanni Di Nardo, Salvatore Oliva, Franca Viola, Salvatore Cucchiara, Angela Santoni, Gabriella Palmieri, Stefania Uccini

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease. PATIENTS AND Methods: Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence-activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real-time polymerase chain reaction. Results: FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase. Conclusions: TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early-onset condition may represent a privileged observatory to dissect the immune-mediated pathogenetic mechanisms at the basis of the disease.

Original languageEnglish
Pages (from-to)563-572
Number of pages10
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume51
Issue number5
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Inflammatory Bowel Diseases
Pediatrics
T-Lymphocytes
Phenotype
Mucous Membrane
Natural Killer T-Cells
Regulatory T-Lymphocytes
Real-Time Polymerase Chain Reaction
Blood Cells
Flow Cytometry
Immunohistochemistry
Inflammation
Messenger RNA
Population

Keywords

  • Crohn disease
  • inflammatory bowel disease
  • natural killer
  • regulatory T cells
  • ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

Cite this

Peripheral and intestinal CD4+ T cells with a regulatory phenotype in pediatric patients with inflammatory bowel disease. / La Scaleia, Raffaella; Morrone, Stefania; Stoppacciaro, Antonella; Scarpino, Stefania; Antonelli, Manila; Bianchi, Elettra; Di Nardo, Giovanni; Oliva, Salvatore; Viola, Franca; Cucchiara, Salvatore; Santoni, Angela; Palmieri, Gabriella; Uccini, Stefania.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 51, No. 5, 11.2010, p. 563-572.

Research output: Contribution to journalArticle

La Scaleia, R, Morrone, S, Stoppacciaro, A, Scarpino, S, Antonelli, M, Bianchi, E, Di Nardo, G, Oliva, S, Viola, F, Cucchiara, S, Santoni, A, Palmieri, G & Uccini, S 2010, 'Peripheral and intestinal CD4+ T cells with a regulatory phenotype in pediatric patients with inflammatory bowel disease', Journal of Pediatric Gastroenterology and Nutrition, vol. 51, no. 5, pp. 563-572. https://doi.org/10.1097/MPG.0b013e3181e4d323
La Scaleia, Raffaella ; Morrone, Stefania ; Stoppacciaro, Antonella ; Scarpino, Stefania ; Antonelli, Manila ; Bianchi, Elettra ; Di Nardo, Giovanni ; Oliva, Salvatore ; Viola, Franca ; Cucchiara, Salvatore ; Santoni, Angela ; Palmieri, Gabriella ; Uccini, Stefania. / Peripheral and intestinal CD4+ T cells with a regulatory phenotype in pediatric patients with inflammatory bowel disease. In: Journal of Pediatric Gastroenterology and Nutrition. 2010 ; Vol. 51, No. 5. pp. 563-572.
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abstract = "Objectives: Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease. PATIENTS AND Methods: Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence-activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real-time polymerase chain reaction. Results: FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase. Conclusions: TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early-onset condition may represent a privileged observatory to dissect the immune-mediated pathogenetic mechanisms at the basis of the disease.",
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AU - La Scaleia, Raffaella

AU - Morrone, Stefania

AU - Stoppacciaro, Antonella

AU - Scarpino, Stefania

AU - Antonelli, Manila

AU - Bianchi, Elettra

AU - Di Nardo, Giovanni

AU - Oliva, Salvatore

AU - Viola, Franca

AU - Cucchiara, Salvatore

AU - Santoni, Angela

AU - Palmieri, Gabriella

AU - Uccini, Stefania

PY - 2010/11

Y1 - 2010/11

N2 - Objectives: Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease. PATIENTS AND Methods: Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence-activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real-time polymerase chain reaction. Results: FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase. Conclusions: TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early-onset condition may represent a privileged observatory to dissect the immune-mediated pathogenetic mechanisms at the basis of the disease.

AB - Objectives: Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease. PATIENTS AND Methods: Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence-activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real-time polymerase chain reaction. Results: FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase. Conclusions: TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early-onset condition may represent a privileged observatory to dissect the immune-mediated pathogenetic mechanisms at the basis of the disease.

KW - Crohn disease

KW - inflammatory bowel disease

KW - natural killer

KW - regulatory T cells

KW - ulcerative colitis

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