Gammadelta T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-alpha and IFN-gamma-producers in response to Pseudomonas aeruginosa

Respir Res. 2003;4(1):9. doi: 10.1186/1465-9921-4-9. Epub 2003 Sep 8.

Abstract

Background: Gammadelta T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation.

Methods: The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-gamma and TNF-alpha production by gammadelta and alphabeta T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA). Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC) culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of gammadelta T cells were also evaluated.

Results: The highest production of cytokine was of TNF-alpha and IFN-gamma, gammadelta being better producers than alphabeta. No differences were found between patients and controls. The Vgamma9delta2 subset of gammadelta T cells was preferentially expanded. CD25 and CD45RO expression by the alphabeta T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes.

Conclusion: Our results support the hypothesis that gammadelta T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / pathology
  • Cytokines / biosynthesis
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / biosynthesis*
  • Intracellular Membranes / metabolism
  • Ionomycin / pharmacology
  • Kinetics
  • Leukocyte Common Antigens / analysis
  • Male
  • Monocytes / pathology
  • Phenotype
  • Pseudomonas Infections / complications*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Ionomycin
  • Interferon-gamma
  • Leukocyte Common Antigens
  • Tetradecanoylphorbol Acetate