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


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.
La Scaleia
Raffaella
R
Department of Experimental Medicine, Sapienza-University of Rome, Italy.
Morrone
Stefania
S
Stoppacciaro
Antonella
A
Scarpino
Stefania
S
Antonelli
Manila
M
Bianchi
Elettra
E
Di Nardo
Giovanni
G
Oliva
Salvatore
S
Viola
Franca
F
Cucchiara
Salvatore
S
Santoni
Angela
A
Palmieri
Gabriella
G
Uccini
Stefania
S
D016022:Case-Control Studies; D002648:Child; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger