Active tuberculosis is characterized by an antigen specific and strictly localized expansion of effector T cells at the site of infection

Eur J Immunol. 2012 Nov;42(11):2844-50. doi: 10.1002/eji.201242678. Epub 2012 Sep 20.

Abstract

Mycobacterium tuberculosis (MTB)-specific cytokine responses in the peripheral blood and at the site of infection may differ significantly within the same individual, but the under-lying T-cell subset changes are largely unknown. Here, we measured effector and memory T-cell markers on CD4⁺ T cells (CD45RO, cysteine chemokine receptor (CCR)7, and CD27) in peripheral blood and at the site of active tuberculosis (TB). Additionally, T cells were stimulated overnight with purified protein derivative (PPD) and early secretory antigenic target (ESAT)-6 to determine which T-cell subset produces MTB-specific interferon (IFN)-γ. A striking decrease in CCR7 and CD27 expression on T cells was noted at the site of active TB. Likewise, IFN-γ expressing, ESAT-6 specific CD4⁺CD45RO⁺CD27⁻ T cells were dramatically increased at the site of infection but were not detectable in peripheral blood. An antigen-specific expansion of differentiated T cells at the site of active TB infection was poorly reflected in peripheral blood. Insight in these changes in MTB-specific effector T cells in different compartments of the body could lead to new approaches for immune-based diagnosis and interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / blood
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Leukocyte Common Antigens / blood
  • Leukocyte Common Antigens / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CCR7 / blood
  • Receptors, CCR7 / immunology*
  • Statistics, Nonparametric
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • Tuberculin / pharmacology
  • Tuberculosis / blood
  • Tuberculosis / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology

Substances

  • Antigens, Bacterial
  • CCR7 protein, human
  • ESAT-6 antigen, Mycobacterium leprae
  • Receptors, CCR7
  • Tuberculin
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma
  • Leukocyte Common Antigens