A key role for lung-resident memory lymphocytes in protective immune responses after BCG vaccination

Lisa M. Connor, Marina C. Harvie, Fenella J. Rich, Kylie M. Quinn, Volker Brinkmann, Graham Le Gros, Joanna R. Kirman

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

The immune mechanisms that orchestrate protection against tuberculosis as a result of BCG vaccination are not fully understood. We used the immunomodulatory properties of fingolimod (FTY720) treatment to test whether the lung-resident memory T lymphocytes generated by BCG vaccination were sufficient to maintain immunity against challenge infection with mycobacteria (BCG). Mice were given daily fingolimod treatment, starting either immediately before s.c. BCG vaccination or during subsequent BCG i.n. challenge, to prevent LN effector and memory lymphocytes from entering the periphery either during priming or challenge, respectively. Treatment with fingolimod during vaccination reduced vaccine-mediated protection against subsequent infection. By contrast, BCG-vaccinated mice were protected when fingolimod was given during the infectious challenge, suggesting that memory lymphocytes that migrate to the lung following vaccination are sufficient for protection. Notably, the antigen-reactive IFN-γ or multicytokine-producing CD4+ T cells present in the lung when fingolimod was given during BCG challenge did not correlate with protection; however, expression of MHC class II on macrophages isolated from the lungs post BCG challenge was increased in the protected mice. We conclude that protection conferred by BCG vaccination is dependent on memory lymphocytes retained in the lung, although IFN-γ production by this population is not correlated with vaccine-mediated protection.

Original languageEnglish
Pages (from-to)2482-2492
Number of pages11
JournalEuropean Journal of Immunology
Volume40
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • BCG
  • FTY720
  • IFN-γ
  • Tuberculosis

Cite this