Enhanced protection conferred by mucosal BCG vaccination associates with presence of antigen-specific lung tissue-resident PD-1 + KLRG1 - CD4 + T cells

Mucosal Immunol. 2019 Mar;12(2):555-564. doi: 10.1038/s41385-018-0109-1. Epub 2018 Nov 16.

Abstract

BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route. Intravascular staining allowed discrimination of lung tissue-resident CD4+ T cells from those in the lung vasculature, revealing that mucosal vaccination resulted in an increased frequency of antigen-specific tissue-resident CD4+ T cells compared to systemic vaccination. Tissue-resident CD4+ T cells induced by mucosal BCG displayed enhanced proliferative capacity compared to lung vascular and splenic CD4+ T cells. Only mucosal BCG induced antigen-specific tissue-resident T cells expressing a PD-1+ KLRG1- cell-surface phenotype. These cells constitute a BCG-induced population which may be responsible for the enhanced protection observed with IN vaccination. We demonstrate that mucosal BCG vaccination significantly improves protection over systemic BCG and this correlates with a novel population of BCG-induced lung tissue-resident CD4+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Humans
  • Lung / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mucous Membrane / immunology*
  • Mycobacterium bovis / immunology*
  • Mycobacterium tuberculosis / physiology*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, Immunologic / metabolism
  • Tuberculosis / immunology*
  • Tuberculosis Vaccines / immunology*
  • Vaccination

Substances

  • Antigens
  • Klrg1 protein, mouse
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • Tuberculosis Vaccines