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

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-alpha 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- 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-alpha 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-alpha mAbs administration along the fistula as a promising tool for the treatment of these patients.