Lymphocyte profile and cytokine mRNA expression in peripheral blood mononuclear cells of patients with recurrent respiratory papillomatosis suggest dysregulated cytokine mRNA response and impaired cytotoxic capacity

Immun Inflamm Dis. 2017 Dec;5(4):541-550. doi: 10.1002/iid3.188. Epub 2017 Aug 14.

Abstract

Objectives: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP.

Methods: We performed a phenotypic characterization of peripheral blood mononuclear cells (PBMC) collected from 16 RRP patients and 12 age-matched healthy controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR cytokine analysis, differentiating between Th1-, Th2-, Th3/regulatory-, and inflammatory immune responses.

Results: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B expressing lymphocytes. There was an overall suppression of cytokine mRNA production and an aberrant cytokine mRNA profile in the activated NK cells.

Conclusion: These findings demonstrate an immune dysregulation with inverted CD4+ /CD8+ ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls.

Keywords: Human; T Cells; natural killer T cells; viral/retroviral.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Case-Control Studies
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic*
  • Female
  • Gene Expression*
  • Human papillomavirus 11
  • Human papillomavirus 6
  • Humans
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Male
  • Papilloma / diagnosis
  • Papilloma / etiology*
  • Papilloma / metabolism
  • Respiratory Tract Neoplasms / diagnosis
  • Respiratory Tract Neoplasms / etiology*
  • Respiratory Tract Neoplasms / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Cytokines