Peripheral regulatory T cells and serum transforming growth factor-β: Relationship with clinical response to infliximab in Crohn's disease

Authors

  • Antonio Di Sabatino MD,

    Corresponding author
    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    • Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Piazzale Golgi 5, 27100 Pavia, Italy
    Search for more papers by this author
  • Paolo Biancheri MD,

    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    Search for more papers by this author
  • Silvia Piconese PhD,

    1. Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
    Search for more papers by this author
  • M. Manuela Rosado PhD,

    1. B-cell Development Lab, Bambino Gesù Pediatric Hospital, Rome, Italy
    Search for more papers by this author
  • Sandro Ardizzone MD,

    1. Gastroenterology Division, Department of Clinical Sciences, Luigi Sacco University Hospital, Milan, Italy
    Search for more papers by this author
  • Laura Rovedatti MD,

    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    Search for more papers by this author
  • Cristina Ubezio MD,

    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    Search for more papers by this author
  • Alessandro Massari MD,

    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    Search for more papers by this author
  • Gianluca M. Sampietro MD,

    1. Surgery Division, Department of Clinical Sciences, Luigi Sacco University Hospital, Milan, Italy
    Search for more papers by this author
  • Diego Foschi MD,

    1. Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK
    Search for more papers by this author
  • Gabriele Bianchi Porro MD,

    1. Gastroenterology Division, Department of Clinical Sciences, Luigi Sacco University Hospital, Milan, Italy
    Search for more papers by this author
  • Mario P. Colombo PhD,

    1. Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
    Search for more papers by this author
  • Rita Carsetti MD, PhD,

    1. B-cell Development Lab, Bambino Gesù Pediatric Hospital, Rome, Italy
    Search for more papers by this author
  • Thomas T. MacDonald PhD, FRCPath, FmedSci,

    1. Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK
    Search for more papers by this author
  • Gino R. Corazza MD

    1. First Department of Medicine, Centro per lo Studio e la Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy
    Search for more papers by this author

  • A.D.S. and P.B. contributed equally to the article and are considered joint first authors; T.T.M. and G.R.C. are considered joint last authors.

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)-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. (Inflamm Bowel Dis 2010)

Ancillary