Digestive Diseases and Sciences

, Volume 56, Issue 12, pp 3525–3533 | Cite as

Th1 Responses Are More Susceptible to Infliximab-Mediated Immunosuppression Than Th17 Responses

  • Kenji Kanayama
  • Kazuhiko Nakamura
  • Haruei Ogino
  • Yorinobu Sumida
  • Eikichi Ihara
  • Hirotada Akiho
  • Ryoichi Takayanagi
Original Article

Abstract

Background

Treatment with infliximab, a chimeric anti-tumor necrosis factor (TNF)-α antibody, is highly efficient in patients with inflammatory bowel disease (IBD). It neutralizes soluble TNF-α and induces the apoptosis of transmembrane TNF-α-positive macrophages and T cells in the gut. Recently, T helper (Th)17, as well as Th1, responses have been implicated in the pathogenesis of IBD.

Aims

To clarify the effects of infliximab on Th1 and Th17 responses in vitro.

Methods

Naive CD4+ T cells isolated from the peripheral blood of healthy volunteers were stimulated under Th1- or Th17-inducing conditions in the presence of 10 μg/ml of infliximab or control immunoglobulin (Ig)G1. The concentrations of interferon (IFN)-γ, interleukin (IL)-17, and TNF-α in the culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Th1 and Th17 cells were immunostained with infliximab or control IgG1 and transmembrane TNF-α-positive cells were analyzed by flow cytometry. Annexin V staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays were conducted in order to analyze the percentage of apoptotic cells.

Results

Both Th1 and Th17 cells expressed soluble and transmembrane TNF-α abundantly. Although infliximab suppressed IFN-γ secretion by Th1 cells and IL-17 secretion by Th17 cells, the level of the former was more profound than the latter. Infliximab increased annexin V- and TUNEL-positive apoptotic cells under Th1-inducing conditions, but not under Th17-inducing conditions.

Conclusions

Infliximab suppressed Th1 and Th17 differentiation in vitro; however, IFN-γ production by Th1 cells was more profoundly suppressed than IL-17 secretion by Th17 cells. Th1 responses were more susceptible to infliximab-mediated apoptosis than Th17 responses. Our results clarify a new mechanism of action of infliximab.

Keywords

Infliximab Tumor necrosis factor-α T helper 1 T helper 17 Apoptosis 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kenji Kanayama
    • 1
  • Kazuhiko Nakamura
    • 1
  • Haruei Ogino
    • 1
  • Yorinobu Sumida
    • 1
  • Eikichi Ihara
    • 1
  • Hirotada Akiho
    • 1
  • Ryoichi Takayanagi
    • 1
  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical SciencesKyushu UniversityHigashi-kuJapan

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