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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

Journal of Pediatric Gastroenterology & Nutrition: November 2010 - Volume 51 - Issue 5 - p 563–572
doi: 10.1097/MPG.0b013e3181e4d323
Original Articles: Gastroenterology

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.

*Department of Experimental Medicine, Italy

Department of Clinical and Molecular Medicine, Italy

Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza–University of Rome, Italy.

Received 29 May, 2009

Accepted 23 April, 2010

Address correspondence and reprint requests to Stefania Uccini, MD, Department of Clinical and Molecular Medicine, II Medical School, Sapienza–University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy (e-mail:

Drs Palmieri and Uccini contributed equally to this article.

Grant support: “Progetti di Ricerca di Ateneo” 2005 to 2007 and “Progetti Coordinati di Ateneo Federato delle Scienze delle Politiche Pubbliche e Sanitarie (SPPS)” 2008.

The authors report no conflicts of interest.

Copyright 2010 by ESPGHAN and NASPGHAN