Subunit vaccine H56/CAF01 induces a population of circulating CD4 T cells that traffic into the Mycobacterium tuberculosis-infected lung

Mucosal Immunol. 2017 Mar;10(2):555-564. doi: 10.1038/mi.2016.70. Epub 2016 Aug 24.

Abstract

The capacity of CD4 T cells to protect against Mycobacterium tuberculosis (Mtb) is governed by their ability to localize to the lung site of infection. Subunit vaccine H56/CAF01, a liposome-adjuvanted fusion protein of Mtb antigens Ag85B, ESAT-6, and Rv2660, conferred durable protection and elicited polyfunctional CD4 T cells that preferentially localized to the lung parenchyma. These lung-resident T cells had reduced KLRG1 and increased CXCR3 expression, an intermediate state of Th1 differentiation that has been associated with Mtb protection. Importantly, KLGR1- CXCR3+ cells were also enriched in the lung vasculature and peripheral circulation of vaccinated animals, but not controls. Moreover, S1P1R blockade rapidly cleared this population from the blood and adoptive transfer of T cells recovered from the vasculature of vaccinated, but not control, mice efficiently trafficked into the Mtb-infected lung parenchyma. Thus, durable immunity elicited by H56/CAF01 vaccination is associated with the maintenance of circulating CD4 T cells that selectively home to the lung parenchyma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Animals
  • Antigens, Bacterial / genetics
  • Bacterial Proteins / genetics
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Humans
  • Lung / immunology*
  • Lung / microbiology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CXCR3 / metabolism
  • Receptors, Immunologic / metabolism
  • Receptors, Lysosphingolipid / antagonists & inhibitors
  • Th1 Cells / immunology*
  • Th1 Cells / microbiology
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Subunit / genetics

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cxcr3 protein, mouse
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Klrg1 protein, mouse
  • Receptors, CXCR3
  • Receptors, Immunologic
  • Receptors, Lysosphingolipid
  • Rv2660c protein, Mycobacterium tuberculosis
  • Tuberculosis Vaccines
  • Vaccines, Subunit
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis