CD4+CD161+ T lymphocytes infiltrate Crohn's disease-associated perianal fistulas and are reduced by anti-TNF-α local therapy

Int Arch Allergy Immunol. 2013;161(1):81-6. doi: 10.1159/000343467. Epub 2012 Dec 15.


Background: Crohn's disease (CD) is an idiopathic inflammatory bowel disease (IBD) in the pathogenesis of which both Th1 and Th17 lymphocytes have been described as being involved. The NK-associated molecule CD161 has recently been described as a marker of IL-17-producing lymphocytes. In this work we assessed the presence and the functional features of CD161 T helper lymphocytes infiltrating CD-associated perianal fistulas, both before and after inoculation of anti-TNF-α mAbs along the fistula.

Methods: In a group of 9 CD patients with fistulizing perianal disease, we evaluated phenotypic and functional features of T cells recovered from the fistula, comparing them with peripheral blood (PB) T lymphocytes. Moreover, the effects anti-TNF-α mAbs injections along the fistula in terms of ability to reduce the inflammatory infiltrate and to determine fistula disappearance were assessed.

Results: In CD patients with fistulizing disease there is an accumulation of CD161+ T helper lymphocytes, with higher frequencies of Th1, Th17 and Th17/Th1 cells in the fistula than in PB. Local anti-TNF-α administration is associated with fistula resolution in the majority of patients with disappearance of infiltrating T lymphocytes, without any systemic effect in circulating effector T cells.

Conclusions: These findings suggest that CD4+CD161+ T cells with Th17, Th17/Th1 and Th1 phenotype accumulate in CD perianal fistulas, and indicate local anti-TNF-α mAbs administration along the fistula as a promising tool for the treatment of these patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily B / immunology*
  • Rectal Fistula / drug therapy*
  • Rectal Fistula / immunology*
  • Rectal Fistula / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • NK Cell Lectin-Like Receptor Subfamily B
  • Tumor Necrosis Factor-alpha
  • Adalimumab