Peripheral regulatory T cells and serum transforming growth factor-β: Relationship with clinical response to infliximab in Crohns disease

Antonio Di Sabatino, Paolo Biancheri, Silvia Piconese, M. Manuela Rosado, Sandro Ardizzone, Laura Rovedatti, Cristina Ubezio, Alessandro Massari, Gianluca M. Sampietro, Diego Foschi, Gabriele Bianchi Porro, Mario P. Colombo, Rita Carsetti, Thomas T. MacDonald, Gino R. Corazza

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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)-?, which is centrally involved in Crohns 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. (Inflamm Bowel Dis 2010)

Original languageEnglish
Pages (from-to)1891-1897
Number of pages7
JournalInflammatory Bowel Diseases
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2010

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Transforming Growth Factors
Regulatory T-Lymphocytes
Crohn Disease
Serum
Interleukin-10
Tumor Necrosis Factor-alpha
Colitis
Coculture Techniques
Infliximab
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Cell Proliferation
Prospective Studies
T-Lymphocytes
Therapeutics

Keywords

  • Foxp3
  • IL-10
  • suppression assay
  • TNF-?

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Peripheral regulatory T cells and serum transforming growth factor-β : Relationship with clinical response to infliximab in Crohns disease. / Di Sabatino, Antonio; Biancheri, Paolo; Piconese, Silvia; Rosado, M. Manuela; Ardizzone, Sandro; Rovedatti, Laura; Ubezio, Cristina; Massari, Alessandro; Sampietro, Gianluca M.; Foschi, Diego; Porro, Gabriele Bianchi; Colombo, Mario P.; Carsetti, Rita; MacDonald, Thomas T.; Corazza, Gino R.

In: Inflammatory Bowel Diseases, Vol. 16, No. 11, 11.2010, p. 1891-1897.

Research output: Contribution to journalArticle

Di Sabatino, Antonio ; Biancheri, Paolo ; Piconese, Silvia ; Rosado, M. Manuela ; Ardizzone, Sandro ; Rovedatti, Laura ; Ubezio, Cristina ; Massari, Alessandro ; Sampietro, Gianluca M. ; Foschi, Diego ; Porro, Gabriele Bianchi ; Colombo, Mario P. ; Carsetti, Rita ; MacDonald, Thomas T. ; Corazza, Gino R. / Peripheral regulatory T cells and serum transforming growth factor-β : Relationship with clinical response to infliximab in Crohns disease. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 11. pp. 1891-1897.
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AU - Piconese, Silvia

AU - Rosado, M. Manuela

AU - Ardizzone, Sandro

AU - Rovedatti, Laura

AU - Ubezio, Cristina

AU - Massari, Alessandro

AU - Sampietro, Gianluca M.

AU - Foschi, Diego

AU - Porro, Gabriele Bianchi

AU - Colombo, Mario P.

AU - Carsetti, Rita

AU - MacDonald, Thomas T.

AU - Corazza, Gino R.

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AB - 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)-?, which is centrally involved in Crohns 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. (Inflamm Bowel Dis 2010)

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