Skewed T-cell receptor variable β repertoire and massive T-cell activation in idiopathic orofacial granulomatosis

Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):503-11. doi: 10.1177/039463201202500221.

Abstract

Orofacial granulomatosis (OFG) is a clinicopathologic entity describing oral lesions with noncaseating granulomas including a spectrum of diseases such as the Melkersson-Rosenthal syndrome. The involvement of abnormal T-cell responses has been suggested in the pathogenesis of OFG although few and contrasting data are currently available on this issue. In a patient with OFG, we observed virtually complete CD4 and CD8 T-cell receptor (TCR) β-chain variable region (BV) repertoires at the lesion level and in circulation. However, oligoclonal profiles were found in CD4 and, to a greater extent, in CD8 subsets. These findings were seen in association with a massive peripheral T-cell activation, decreased naive T cells, reduced thymic output, altered cytokine production, and increased apoptosis. Our data, pointing to a random influx of T cells at the site of inflammation, argue against the hypothesis of a main allergen acting at the level of oral mucosa. The profound dysregulation of the peripheral T-cell compartment suggests that OFG should be regarded as a systemic disorder with localized manifestations.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Apoptosis
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Cytokines / metabolism
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Lip / immunology*
  • Lip / pathology
  • Lymphocyte Activation / immunology*
  • Male
  • Melkersson-Rosenthal Syndrome / diagnosis
  • Melkersson-Rosenthal Syndrome / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta