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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.

Original publication

DOI

10.1038/s41385-018-0109-1

Type

Journal article

Journal

Mucosal Immunol

Publication Date

03/2019

Volume

12

Pages

555 - 564

Keywords

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