Peripheral regulatory T cells and serum transforming growth factor-β: relationship with clinical response to infliximab in Crohn's disease.
BACKGROUND
CD4(+)Foxp3(+) regulatory T cells (Treg) inhibit T-cell proliferation in vitro and are effective in suppressing colitis in mouse models. Tumor necrosis factor (TNF)-α, which is centrally involved in Crohn's disease (CD) pathogenesis, also impairs Treg function. Here we investigated the influence of anti-TNF therapy on Treg frequency and function in CD.


METHODS
Twenty CD patients were treated with infliximab administered at weeks 0, 2, and 6. Blood was collected immediately before the first infusion and after 10 weeks. Treg frequency was quantified by flow cytometry. Treg function was measured using a standard coculture assay. Serum levels of transforming growth factor (TGF)-β1 and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Pretreatment Treg frequency and serum TGF-β1 levels were significantly higher in nonresponder than responder patients. Clinical improvement in 12 CD patients was associated with a significant increase of Treg frequency after 10 weeks. Treg were functionally active before and after treatment with infliximab, both in responder and nonresponder CD patients. In responder patients the restoration of Treg pool was accompanied by a parallel significant increase of serum TGF-β1 and IL-10. No significant change in the elevated Treg or serum TGF-β1 was seen in nonresponder patients.


CONCLUSIONS
This study suggests that there may be a relationship between numbers of Treg in the blood, serum TGF-β1, and response to infliximab; however, further prospective studies are needed.
Di Sabatino
Antonio
A
First Department of Medicine, Centro per lo Studio e Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. a.disabatino@smatteo.pv.it
Biancheri
Paolo
P
Piconese
Silvia
S
Rosado
M Manuela
MM
Ardizzone
Sandro
S
Rovedatti
Laura
L
Ubezio
Cristina
C
Massari
Alessandro
A
Sampietro
Gianluca M
GM
Foschi
Diego
D
Porro
Gabriele Bianchi
GB
Colombo
Mario P
MP
Carsetti
Rita
R
MacDonald
Thomas T
TT
Corazza
Gino R
GR
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000276:immunology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000069285:Infliximab