Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas

Immunity. 2011 May 27;34(5):807-19. doi: 10.1016/j.immuni.2011.03.022. Epub 2011 May 19.

Abstract

Cell-mediated adaptive immunity is critical for host defense, but little is known about T cell behavior during delivery of effector function. Here we investigate relationships among antigen presentation, T cell motility, and local production of effector cytokines by CD4+ T cells within hepatic granulomas triggered by Bacille Calmette-Guérin or Mycobacterium tuberculosis. At steady-state, only small fractions of mycobacteria-specific T cells showed antigen-induced migration arrest within granulomas, resulting in low-level, polarized secretion of cytokines. However, exogenous antigen elicited rapid arrest and robust cytokine production by the vast majority of effector T cells. These findings suggest that limited antigen presentation and/or recognition within granulomas evoke a muted T cell response drawing on only a fraction of the host's potential effector capacity. Our results provide new insights into the regulation of host-protective functions, especially how antigen availability influences T cell dynamics and, in turn, effector T cell function during chronic infection.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigen Presentation*
  • Cell Movement
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Granuloma / immunology*
  • Granuloma / microbiology
  • Liver Diseases / immunology*
  • Liver Diseases / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / immunology*
  • Mycobacterium tuberculosis / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Cytokines